Disease/Health/Uncategorized

Bigger isn’t better: Inflammation Affects on the Brain

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Bigger Isn’t Better: Inflammation Affects on The Brain

Swelling of the brain might seem like a minor concern when it comes to overall brain health, but inflammation affects homeostasis, disrupting processes such as hunger regulation and metabolism. Hypothalamic inflammation leads to issues such as overeating, energy imbalance, and systemic health issues like diabetes and heart disease. Inflammation is the silent driver of metabolic dysfunction that produces diabetes.

Low-grade inflammation is often caused by obesity, which weakens signaling and disrupts metabolic homeostasis. This type of signaling is labeled as anorexogenic signaling which contributes to fat cell mass and has an affect on the relationship between food intake and energy expenditure. As shown in Figure 1., when anorexigenic signaling decreases, orexigenic signal increases which signals the body to increase appetite and food intake. On the other hand, anorexigenic signaling lowers food intake. Diet also plays a significant role in inflammation. A high fat diet (HFD) or low fat diet (LFD) can affect this signaling in a positive or negative way.[1]

 

gastrointestinal vagal afferent fibres ...
Figure 1. Anorexigenic versus Orexigenic signaling in inflammation and fat gain/loss

 

How Hypothalamic Inflammation Develops

Hypothalamic inflammation is chronic inflammation that affects the hypothalamus region the most, this region is in charge of regulating energy, balance and bodily functions that contribute to homeostasis.

Two hormones, Insulin and Leptin, are major players in how hypothalamic inflammation develops. Leptin is a hormone that is secreted by adipose tissue, AKA body fat, which stores energy. Leptin contributes to Insulin resistance; elevated levels of Leptin are typically due to an increased fat mass. Insulin resistance interferes with Leptin’s normal function: maintaining energy by suppressing hunger. Leptin’s job is to signal to the brain when energy storage is in primal conditions. When Leptin contributes to Insulin resistance it disrupts the glucose metabolism and promotes fat accumulation. There are a multitude of diseases that  contribute to hypothalamic inflammation as shown in Figure 2. 

Figure 2. Factors that contribute to hypothalamic inflammation such as, disease, factors, and cellular mechanisms involved.

 

The blood–brain barrier (BBB) acts as security, regulating the transport of the metabolic signals we receive from the central nervous system (CNS). Disruptions in BBB function can contribute to metabolic and neurological disorders, such as obesity and metabolic syndrome. Elevated triglyceride levels have been shown to impair Leptin transport across the BBB, inducing peripheral Leptin resistance and weakening the brain’s ability to regulate energy homeostasis. Similarly, chronic inflammation and Insulin resistance can alter theBBB strength, affecting cognitive functioning and increasing the chance of neurodegenerative diseases such as Alzheimer’s.[2]

This type of systemic metabolic dysfunction contributes to cognitive and neurological impairments, highlighting the need for targeted interventions to restore metabolic balance and brain health.

Chronic inflammation in the hypothalamus plays a critical role in metabolic dysfunction. There are two main signaling pathways involved:

c-Jun N-terminal kinase (JNK)

IκB kinase (IKK)

These kinases are activated in response to metabolic stress, including excessive nutrient intake, obesity, and Insulin resistance. JNK activation interferes with Insulin signaling by phosphorylating IRS-1, a key mediator in the Insulin pathway, contributing to Insulin resistance and Leptin dysfunction.

Similarly, IKK plays a pivotal role in activating NF-κB, a transcription factor that drives inflammatory responses, further disrupting metabolic homeostasis and impairing brain function.

Elevated activity of these pathways not only exacerbates hypothalamic inflammation but also impairs blood-brain barrier integrity, influencing cognitive function and neurodegenerative disease risk. Understanding how JNK and IKK contribute to metabolic inflammation offers valuable insight into the mechanisms driving obesity, Insulin resistance, and associated neurological disorders.

YUM! Saturated Fatty Acids

We have a general idea of what foods are unhealthy versus heathy. What we choose to put in our bodies develops habits that determine our overall health. It is important to treat your body well and keep your body happy. Studies show that the influence diet has affects not only your body, but also your brain. The response is negative or positive based on what you feed it.

LFD

A low-fat diet (LFD) prioritizes reducing saturated fats, AKA your dietary fat, as shown in Figure 3. While recommended for heart health and weight management, newer research suggests that fat quality matters more than quantity. Some fats, like omega-3 fatty acids, support brain health, while excessive intake of unhealthy fats can promote inflammation and Insulin resistance as shown is Figure 4.

Depreciate those Extra Calories” -Go with the best diet… – Nutrition Meets Food Science
Figure 3.

Acute HFD

Short-term exposure to a high-fat diet (HFD) has been shown to disrupt normal metabolic processes, leading to temporary Insulin resistance and increased inflammatory markers. In animal studies, acute HFD exposure has been linked to impaired Leptin signaling, weakening the brain’s ability to regulate hunger and energy balance.

Chronic HFD

Long-term consumption of a high-fat diet presents more severe consequences. Chronic HFD has been extensively studied for its role in promoting obesity, metabolic dysfunction, and neuroinflammation. Continued exposure to excessive saturated fatty acids contributes to the risk of hypothalamic inflammation, disrupting Leptin and Insulin signaling, impairing the BBB strength, and increasing the risk of neurodegenerative diseases. [3]

Figure 4. Good fats versus bad fats

The Melanocortin System and Energy Regulation

The melanocortin system is involved in various physiological processes, including energy balance, immune regulation, and pigmentation. This complex network comprises melanocortin peptides derived from pro-opiomelanocortin (POMC), five melanocortin receptors (MCRs), and two endogenous antagonists—agouti-signaling protein and agouti-related peptide. Research has discovered the importance of this system and its broader influence on inflammation, metabolic regulation, and neural signaling.

The melanocortin system consists of  three important players: POMC, AgRP, and FOXO1 neurons.

POMC neurons

The activity of POMC neurons is tightly regulated by various signals, including Leptin and Insulin, which contributes to promote satiety. POMC neurons are functionally opposed by AgRP neurons, which exert antagonistic effects on melanocortin signaling by inhibiting MC3R and MC4R activity, promoting hunger and reducing energy expenditure.[4]

AgRP neurons

Agouti-related peptide (AgRP) is primarily involved in regulating appetite, energy balance, and promoting food intake. Melanocortin receptors, MC3R and MC4R, take part in metabolism and food intake. By binding to these receptors, AgRP effectively suppresses melanocortin signaling, leading to increased feeding behavior and reduced energy expenditure, as shown in Figure 5. 

FOXO1

AgRP’s role in metabolism and energy balance is closely linked to transcription factors that regulate cellular processes, including FOXO1. FOXO1 (Forkhead box protein O1) is a key transcription factor involved in Insulin signaling, gluconeogenesis, AKA the process where the liver and kidneys make sugar, and neuroendocrine regulation.

When energy levels are low, FOXO1 becomes more active and enhances AgRP gene transcription, promoting appetite stimulation and increasing food intake. This interaction is crucial in energy deficient states, such as fasting or caloric restriction, where the body prioritizes nutrient intake and conservation. Conversely, Insulin signaling inhibits FOXO1 activity, reducing AgRP expression and suppressing hunger.[5]

Figure 6.
Figure 6. Artwork of metabolic brain

The Brain is #1

The brain is the most important part of our bodies. It is responsible for everything that we are able to do. Protecting our brain and prioritizing brain health means making healthy choices that support our metabolic balance and minimize inflammation. A high-fat diet, when sustained over time, not only leads to obesity but also fuels Insulin resistance and inflammatory processes that compromise brain health. This type of damage can be avoided with lifestyle changes by prioritizing anti-inflammatory nutrients.We can improve metabolic flexibility by choosing whole, nutrient-dense foods. By making healthy choices, we set a foundation for long-term physical and cognitive resilience.

 

REFRENCES

Banks WA, Farr SA, Salameh TS, Niehoff ML, Rhea EM, Morley JE, Hanson AJ, Hansen KM, Craft S. Triglycerides cross the blood-brain barrier and induce central leptin and insulin receptor resistance. Int J Obes (Lond). 2018 Mar;42(3):391-397. doi: 10.1038/ijo.2017.231. Epub 2017 Oct 9. PMID: 28990588; PMCID: PMC5880581.

Henn, R. E., Elzinga, S. E., Glass, E., Parent, R., Guo, K., Allouch, A. M., Mendelson, F. E., Hayes, J., Webber-Davis, I., Murphy, G. G., Hur, J., & Feldman, E. L. (2022). Obesity-induced neuroinflammation and cognitive impairment in young adult versus middle-aged mice. Immunity & ageing : I & A, 19(1), 67. https://doi.org/10.1186/s12979-022-00323-7

Jais, A., & Brüning, J. C. (2017, January 3). Hypothalamic inflammation in obesity and metabolic disease. The Journal of clinical investigation. https://pmc.ncbi.nlm.nih.gov/articles/PMC5199695/

Kentish, S.J. and Page, A.J. (2015), The role of gastrointestinal vagal afferent fibres in obesity. J Physiol, 593: 775-786. https://doi.org/10.1113/jphysiol.2014.278226

Wang, W., Guo, D. Y., Lin, Y. J., & Tao, Y. X. (2019). Melanocortin Regulation of Inflammation. Frontiers in endocrinology, 10, 683. https://doi.org/10.3389/fendo.2019.00683

 

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Potential Pathways to Escape Brain Cancer

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Do you know what types of cancer are more likely to kill you? Do you know how to avoid contracting or how to treat these? Unfortunately, some cancers are more deadly than others, these tending to be the types whose course of disease is unpredictable, making their effective treatment rather unknown. Glioblastoma (GBM) is one such cancer, it being a lethal, malignant form of brain cancer that usually kills its host within 2 years if not less. Luckily though, recent research into how different cellular signaling pathways regulate tumor growth in GBM has shown promise in identifying ways to treat cancers like GBM. Here, we’ll discuss this topic and how regulating two molecules, the cAMP Response Element Binding Protein (CREB) and the BCL2-Like 11 (for short, “Bim”) protein, may fight the growth of cancer.

 

What Makes GBM So Complicated?

Part of what makes GBM, and other alike cancers, so hard to treat is that fact that are multiple types of GBM, and this impacts what the best course of treatment is. In addition, one type, called Neural GBM, has no obvious pattern when it comes to when genes it causes mutation to, making the survival rates of those with GBM very low. However, the fact that GBM causes mutations in a differing number of genes seems to be the common thread amongst all types.1

 

What Pathways May Be Involved in GBM

Figure 1. This illustrates how the MAPK, PI3K, and cAMP pathways regulate the activity of CREB, with asterisks indicating potential places for drug treatments.1

And these genes impact the expression of different pathways within neurons. With mesenchymal GBM, certain mutations lead to dysfunction of the mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase (PI3K) pathways, which ultimately end up impacting what genes in a neuron are transcribed by regulating activity of cAMP Response Element Binding Protein (CREB), seen in Figure 1. CREB is called a transcription factor for this reason, and when its activity is upregulated in cases of GBM that disrupt the MAPK and PI3K pathways, is dysregulates the activity of typical proteins, causing tumor cell growth and irregular neuron development.1

Also seen in Figure 1 is how CREB activity is also regulated by the cyclic adenosine 3′,5′-monophosphate (cAMP) pathway. Opposite to the MAPK and PI3K pathways, cAMP has a low level of activation in tumor growths, so researchers hypothesize that elevating it would inhibit tumor growth.1 For more in-depth information on how treating different aspects of each pathway may degrade tumors, see [here].

 

The cAMP Pathway & Its Involvement in GBM

Figure 2. This displays the cAMP pathway and molecules, like Fsk, and PDEi, that would lead to its increased activation.1

Low cAMP levels are positively correlated with tumor malignancy, making it a promising target for cancer treatments. Research suggests that enzymes that work to activate cAMP, like forskolin (Fsk) and phosphodiesterase inhibitor (PDEi), would be effective.1 These are illustrated in Figure 2, and for more information on how they work, see [here].

But what makes the cAMP pathway cause tumor cell death? Well, research has shown that it may be due to its activity increasing the expression of Bim.

 

Bim & How it Impacts Tumor Growth in GBM

Figure 3. This displays the impact of stress signals on the expression of Bim proteins and their impact on the mitochondria.2

 

In mammals, Bim proteins directly interact with Bak and Bax, two pro-apoptotic proteins, meaning they induce cell death. They do this by increasing the mitochondrial outer membrane (MOM) permeability, demonstrated in Figure 3. This allows things to enter or exit the mitochondria that shouldn’t and initiates apoptotic pathways, thus causing cell death.2

Not only does expression of the Bim gene through its interaction with pro-apoptotic proteins, but it also acts to increase cell death by:

  1. Neutralizing the anti-apoptotic BCL-2 proteins, or…
  2. Uncoupling mitochondrial respiration, causing an increase in cellular levels of reactive oxygen species (ROSs).2

For more information on the pathways by which Bim works and what stimuli initiates its activation, see [here], and for a review on what the MOM does for the cell, watch this video: [MOM].3

 

How Bim Activation Can Be Used to Treat GBM

Bim typically is transcribed in response to certain stimuli independent of CREB, but in some cancer patients, the transcription of it and the creation of its Bim proteins may be decreased. So, if Bim levels can be increased in tumor cells, this may lead to their death in patients with GBM and alike cancers.2

Interestingly, the MAPK pathway inhibits Bim-regulated apoptosis as well, promoting tumor cell growth. So, Bim agonists may also be considered in GBM patients whose MAPK pathways are overly activated to induce tumor cell death.2

 

Conclusion

In conclusion, CREB activity is regulated by the PI3K, MAPK, and cAMP pathways, but the cAMP pathway’s activation of CREB leads to the creation/activation of proteins different than the MAPK and PI3K pathways. Therefore, if doctors and researchers can determine which pathway is disrupted in patients with GBM, they can administer treatment that directly targets the root of the problem, and this applies to all types of cancer. In the example of the cAMP pathway, it’s been shown that increased Bim expression leads to death of cancer cells, so in such patients where it is the cAMP pathway being disrupted, Bim activators may be effective treatments against GBM that don’t cause the side effects that a CREB inhibitor might, as Bim acts independently of CREB. Further research needs to be done on this topic, but ultimately, research on the genes involved in tumor cell growth provides a promising explanation as to why they occur and how we could possibly treat them without invasive treatments such as chemotherapy.

 

Footnotes:

1Fung, N.H, et. al. “Understanding and exploiting cell signaling convergence nodes and pathway cross-talk in malignant brain cancer.” Cellular Signaling, vol. 57, 2019, https://doi.org/10.1016/j.cellsig.2019.01.011

2Sionov, R.V., et. al. “Regulation of Bim in Health and Disease.” Oncotarget, vol. 6, no. 27, 2015, https://www.oncotarget.com/article/5492/text/

3Gauthier, Nicholas. “Outer Mitochondrial Membrane; Overview and Function.” Study.com, 2025, https://study.com/learn/lesson/video/outer-mitochondrial-membrane-function-layers-composition.html

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The Silent Saboteur: How Brain Inflammation Could Be Fueling the Obesity Epidemic

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For decades, we’ve pointed fingers at willpower and calories in the battle against obesity. Eat less. Move more. Sounds simple, right?

But what if we’ve been missing a critical piece of the puzzle all along – something hidden deep within the brain? What if, instead of a lack of self-control, the true culprit behind rising obesity rates is inflammation in the brain itself?

A Crisis Hiding in Plain Sight

Obesity is no longer just a personal health concern – it’s a global epidemic. Despite the flood of diet plan, exercise apps, and miracle weight-loss pills, the numbers keep climbing. And while conventional wisdom tells us it’s all about lifestyle choices, a growing body of research is challenging that narrative.

One groundbreaking shift in our understanding comes from the field of neuroscience, where researchers have begun investigating how inflammation in the brain – specifically, in a region called the hypothalamus – might be silently sabotaging our efforts to maintain a healthy weight. [1]

Meet Your Brain’s Control Center

Think of the hypothalamus as your body’s internal thermostat for energy (Figure 1). This small but mighty structure regulates hunger, satiety (that feeling of fullness), body temperature, and metabolism. It’s constantly receiving signals from hormones like leptin and insulin, helping the body make smart decisions about when to eat and when to stop. But when this delicate system in thrown off by chronic inflammation, the entire process goes haywire. [2]

Hypothalamus: What It Is, Function, Conditions & Disorders

Figure 1 [3] The hypothalamus helps manage your body temperature, hunger and thirst, mood, sex drive, blood pressure and sleep.

The Hidden Fire Within

Recent studies, like the one reviewed by researchers Jais and Burning, have illuminated how brain inflammation may play a far more active role in obesity than we ever imagined. Here’s what the science reveals:

  1. It starts sooner than you think: Within just days of switching to a high-fat diet, signs of inflammation begin to appear in the hypothalamus. This inflammation doesn’t wait for the number on the scale to climb – it often precedes noticeable weight gain. In other words, the damage may begin before you even realize anything is wrong. [1]
  2. Brain cells join the battle: Under normal conditions, cells in the brain known as microglia and astrocytes act as its maintenance crew, keeping things clean and running smoothly. But when exposed to excess dietary fat, these cells go into overdrive. They start pumping out inflammatory molecules like TNF-alpha and IL-6, which begin to damage the neurons responsible for hunger and metabolism regulation (Figure 2). [1]
  3. Hormonal static: As inflammation ramps up, your hypothalamus starts to lose its ability to respond to leptin and insulin – two critical hormones that tell your brain, “We’ve got enough energy; we don’t need more food.” With this signaling broken, the brain keeps shouting for food, even when the body is full. The result? A cycle of overeating, insulin resistance, and further weight gain (Figure 2). [1]

Figure 2 [1] Cellular network of hypothalamic inflammation.

Why This Matters (More Than You Might Think)

This isn’t just fascinating science – it’s deeply personal. Millions of people struggle with their weight despite eating well, exercising regularly, and following medical advice. And when the pounds don’t budge, the default explanation is often self-blame.

But what if the issue isn’t a lack of effort – but an inflamed brain working against you?

Understanding the role of hypothalamic inflammation reframes the entire conversation. It removes the stigma and shame so often attached to obesity and offers a new lens: what if your Brian is just trying to protect you, but got its are crossed along the way?

Need some further explanation? Watch this video by Yuri Elkaim:

A New Path Forward

The good news is that this research doesn’t just point out a problem – it also lights the way to potential solutions. Scientists are now exploring treatments aimed at reducing inflammation in the brain as a way to restore proper metabolic function. [1]

Early animal studies show that compounds like IL-10 agonists – which help cool down brain inflammation – could reverse some of the hypothalamic damage, improve insulin sensitivity, and even normalize appetite signals. It’s still early days, but the implications are enormous. [4]

Hope on the Horizon

There’s still so much we don’t understand about the intricate dance between brain, body, and metabolism. But one thing is becoming clear: the old narrative about willpower and laziness no longer holds up.

Obesity isn’t just a simple math problem of calories in and out. It’s a complex neurobiological condition, influenced by inflammation, hormones, and brain function (Figure 3). And by looking deeper – literally, into the brain – we can start to craft smarter, more compassionate solutions. [1]

Obesity-induced inflammation: connecting the periphery to the brain | Nature Metabolism

Figure 3 [5] Illustrates how chronic inflammation affects multiple organs, disrupting hormone signaling, immune responses, and metabolism, which collectively contribute to obesity and metabolic disease.

So the next times someone tells you “just eat less and exercise more,” remember this…the real fight might not be in your fridge or at the gym… it might be happening deep inside your brain.

References

[1] Jais, A., & Brüning, J. C. (2017). Hypothalamic inflammation in obesity and metabolic disease. Journal of Clinical Investigation, 127(1), 24–32. https://doi.org/10.1172/jci88878

[2] Yeung, A. Y. (2023, January 3). Physiology, obesity neurohormonal appetite and Satiety Control. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK555906/

[3] professional, C. C. medical. (2025, March 3). Hypothalamus: What it is, function, conditions & disorders. Cleveland Clinic. https://my.clevelandclinic.org/health/body/22566-hypothalamus

[4] Ropelle ER, et al. IL-6and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and septic sensitivity through IKKbeta and ER stress inhibition. PLoS Biol. 2010;8(8):e1000465.

[5] Le Thuc, O., & García-Cáceres, C. (2024, July 12). Obesity-induced inflammation: Connecting the periphery to the brain. Nature News. https://www.nature.com/articles/s42255-024-01079-8

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It’s about time you’ve met your metabolism

Posted on by rhurley1 / 0 Comment

The article we have covered in a previous week, “Hypothalmic inflammation in obesity and metabolic disease” by Alexander Jais and Jens C. Brüning was an article about metabolic inflammation being connected to obesity in many surprising ways. Basically, we know already that obesity is an obstacle for the brain and it’s functioning. However, due to this feature, this is in a way how this correlation works.The topic today is why people should care about this topic and what the people must know, so without further ado let’s get reading!

The article informs us of a typical metabolic homeostasis, and then what happens to it under insulin and leptin resistance. Though, the article specifically focuses mainly on the insulin and leptin resistance aspect. As a result of this connection, we can now at least suspect the connection!

Figure one, pictured above, from the article mentioned above is especially excellent at explaining this where it was needed (excellently timed, or in other words placed well). That piece is a diagram expressing exactly this. The myriad, but consistent colors complements the black parts which either crosses something out, or is a metaphorical old-timey scale. Although, one slight problem could be that it could feel a large bunch overwhelming if you’re not too familiar with the applied terms of figure one in the Neuroscience field. This was an excellent piece to me for it is maximized simplicity because, for clear reasons, that kind of thing strongly helps. The figure may also benefit people uninvolved in Neuroscience as well because figure one uses so much brief, yet descriptive, labeling, and I find that effective myself in general because it’s easy on the eyes to track or logicate.

Now, at this point, one, such as yourself, may wonder why people really should care about all the above information. Well, let’s answer with essential basics to answer ourselves by quickly asking ourselves something simpler first; what really is metabolism? Well, the answer is absolutely nothing short of deeply important. According to Arturo Sánchez López de Nava and Avais Raja, metabolism is known as “the whole sum of reactions that occur throughout the body within each cell and that provide the body with energy.” (Arturo Sánchez López de Nava and Avais Raja 2022).^2 Considering what we know about energy, the ability to do action internally and externally, it’s no shock to pretty much anyone that such a scenario can turn serious fast. Let us put this into perspective with another topic.

In my class, I personally examined the various effects that the person with a penis has in the impact of their child’s birth via their diet. Surprisingly, I learned from the University of Tennessee Institute of Agriculture, even very specific nutritional choices have a direct effect on the child. Using protein as an example, a low amount of protein may cause a higher birth weight while high amounts of protein may lead to glucose intolerance in their child.^3 It is little short of incredible how essential our nutritional choices are, and even more so that we seemingly take little worry to what it does to us.

References:
1) “Hypothalmic inflammation in obesity and metabolic disease” by Alexander Jais and Jens C. Brüning
2)https://www.ncbi.nlm.nih.gov/books/NBK546690
3) https://animalscience.tennessee.edu/wp-content/uploads/sites/7/2022/05/Relevant-Repro-Blog-7_-Paternal-Impacts.pdf

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Rewire Your Metabolism: How Healthy Fats Heal Insulin and Leptin Resistance

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Figure 1: Illustrates how brain inflammation contributes to leptin and insulin resistance, with unsaturated fats helping to reduce inflammation and improve metabolism. Created by Sharleen Mtesa.

We’ve all heard the saying “you are what you eat,” but when it comes to hormones like insulin and leptin, that couldn’t be more true. These two messengers have a big job: insulin helps manage your blood sugar, and leptin tells your brain when you’re full. These two hormones play a critical role in keeping our metabolism on track. And when they’re working properly, they help us maintain a healthy balance between hunger and energy.

But when our diets are high in processed foods, unhealthy fats, and sugar, these hormones can stop functioning correctly. That’s when insulin and leptin resistance kicks in leading to constant cravings, weight gain, and blood sugar issues.

Therefore, incorporating healthy unsaturated fats into your diet like those found in olive oil, avocados, nuts, and fatty fish can be a game-changer. These fats help reduce inflammation, improve hormone sensitivity, and support your body’s ability to manage hunger and energy more effectively. Let’s take a closer look at how these fats actually work to restore balance and boost your health.

How Inflammation Disrupts Insulin and Leptin Resistance.

According to the paper “Hypothalamic Inflammation in Obesity and Metabolic Disease,” a high-fat diet (HFD) triggers inflammation in the hypothalamus, impairing how the brain responds to key hormones like insulin and leptin. This inflammation leads to insulin resistance, which makes it harder for the body to manage blood sugar, and leptin resistance, which disrupts the brain’s ability to signal when you’re full, ultimately increasing hunger and food intake.[1]

The inflammatory process involves the activation of proinflammatory cytokines, like TNF-α, that interfere with insulin and leptin signaling. This damage to hormone function results in metabolic imbalances, weight gain, and constant cravings. These effects on hunger and energy regulation create a vicious cycle, making it harder to maintain a healthy weight and manage blood sugar levels

How Unsaturated Fatty Acids Help Reverse Insulin and Leptin Resistance.

Unsaturated fatty acids, particularly monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs), play a very important role in restoring metabolic balance. These healthy fats not only help with weight control but also improve the body’s response to insulin and leptin by reducing inflammation and promoting fat metabolism.

  • Monounsaturated fats (MUFAs): Found in olive oil, nuts, and avocados.
  • Polyunsaturated fats (PUFAs): Especially omega-3s and omega-6s, found in fatty fish, flaxseeds, and walnuts.

1. Improving Insulin Sensitivity.

Insulin helps cells absorb glucose from the blood, but when the body becomes resistant, blood sugar levels rise, contributing to type 2 diabetes. Unsaturated fats aid in restoring insulin sensitivity in the following ways:

  • Better Cell Membrane Function: Unsaturated fats become part of cell membranes, making them more flexible and fluid. This improves insulin receptor function, allowing glucose to enter cells more efficiently.
  • Reduced Inflammation: Chronic inflammation, often caused by a diet high in saturated fats and processed foods, disrupts insulin signaling. Omega-3s have powerful anti-inflammatory effects, reducing inflammation and improving insulin function. These omega-3s help calm the immune system, prevent activation of inflammatory receptors, and reduce the production of TNF-α, a cytokine that contributes to insulin resistance.
  • Fewer Toxic Fats in Organs: Excess fat storage in organs like the liver and muscles leads to insulin resistance (lipotoxicity). Unsaturated fats help reduce fat accumulation and promote healthy fat metabolism, encouraging the body to use fat for energy instead of storing it in organs. For example, oleic acid (found in olive oil) and omega-3s help reduce diacylglycerol (DAG) buildup in the liver, which is linked to insulin resistance.
  • Gene Regulation: Unsaturated fats activate proteins (like PPARs) [2] that regulate how the body uses sugar and fat, improving glucose control and reducing fat storage.

Figure 2: Insulin Signaling Pathway
This figure shows how insulin activates signaling pathways like PI3K/Akt and MAPK to promote glucose uptake, glycogen synthesis, and cell growth, while SOCS proteins regulate the response through negative feedback.[3]

2. Restoring Leptin Sensitivity

Leptin is produced by fat cells and signals the brain when you’re full. However, in leptin resistance, the brain doesn’t respond, leading to overeating and fat storage. Unsaturated fats help restore leptin sensitivity by:

  • Calming Brain Inflammation: High-fat, high-sugar diets cause inflammation in the brain, especially in the hypothalamus, where leptin acts. Omega-3s help reduce this inflammation, allowing leptin signals to reach the brain effectively.
  • Helping Leptin Cross the Blood-Brain Barrier: Leptin travels from the blood to the brain across the blood-brain barrier. Chronic inflammation can disrupt this process. Omega-3s help improve blood-brain barrier function, enabling leptin to reach the brain more efficiently.
  • Improving Leptin Signaling: Unsaturated fats support better leptin receptor function and reduce the expression of SOCS3, a protein that blocks leptin signaling. As a result, the brain can detect leptin properly, helping to reduce hunger and cravings.[4]

Figure 3: Overview of Leptin Signaling Pathway.
This figure shows the leptin signaling pathway, where leptin activates JAK2, leading to phosphorylation of key sites (pY985, pY1138) and triggering downstream signals like STAT3, PI3K, and ERK. These pathways regulate hunger and energy balance, with SOCS3 acting as a feedback inhibitor.[5]

Feed Your Hormones Right.

When it comes to balancing your metabolism, hormones like insulin and leptin are key players and what you eat has a huge impact on how well they work. Chronic inflammation from highly-processed foods and unhealthy fats can throw these systems off, leading to cravings, weight gain, and blood sugar spikes.

But the good news? Healthy unsaturated fats like those found in olive oil, avocados, nuts, and fatty fish can help reset the system. By calming inflammation, improving hormone signaling, and supporting better fat metabolism, these fats make it easier for your body to respond to hunger and energy cues the way it’s supposed to.

So instead of fearing fat, focus on the right kinds. A few smart swaps in your daily meals can go a long way in supporting hormone health, boosting energy, and helping you feel your best from the inside out.



 

 

 

 

 

 

Footnotes

[1] Jais, A., & Brüning, J. C. (2017). Hypothalamic inflammation in obesity and metabolic disease. The Journal of clinical investigation, 127(1), 24–32. https://doi.org/10.1172/JCI88878

[2] Varga, T., Czimmerer, Z., & Nagy, L. (2011). PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation. Biochimica et biophysica acta, 1812(8), 1007–1022. https://doi.org/10.1016/j.bbadis.2011.02.014

[3],[5] Howard, J. K., & Flier, J. S. (2006). Attenuation of leptin and insulin signaling by SOCS proteins. Trends in Endocrinology & Metabolism, 17(9), 365–371. https://doi.org/10.1016/j.tem.2006.09.007

[4] Park, H. K., & Ahima, R. S. (2014). Leptin signaling. F1000prime reports, 6, 73. https://doi.org/10.12703/P6-73

 

Disease/Health/Uncategorized

Your Brain on Fat: Why Hypothalamic Inflammation Matters

Posted on by ttiongso / 0 Comment

Most of us know that a high-fat, high-sugar diet can lead to weight gain. Many people are aware of how obesity is linked to type 2 diabetes, heart disease, and other chronic conditions. But here’s something less commonly known: the food we eat can trigger inflammation in the brain within just a few days, before we even see a change on the scale.

That’s the core insight from the article “Hypothalamic inflammation in obesity and metabolic disease”. This research shows that the brain, particularly the hypothalamus, isn’t just passively responding to weight gain. Instead, it plays an active role in the development of obesity and related diseases.

The Hypothalamus: A Key Player in Energy Balance

Fig 1
Fig 1 [1]

The hypothalamus is a critical region of the brain responsible for regulating hunger, satiety, and overall energy expenditure[1]. As shown in Figure 1, it contains two key types of neurons: POMC neurons, which help reduce appetite, and AgRP neurons, which stimulate it. Under normal conditions, these neurons respond to signals from hormones like insulin and leptin to maintain balance between energy intake and use[1].

However, diets high in saturated fats—particularly palmitic and stearic acids—can disrupt this system quickly. These fatty acids can cross the blood-brain barrier and accumulate in the hypothalamus. Once there, they activate inflammatory pathways like TLR4 and NF-kB, triggering cellular stress and impairing the brain’s ability to respond to leptin and insulin[1]. Essentially, the brain stops receiving the “I’m full” signal, which promotes overeating and weight gain, even before visible changes in body weight occur[1].

Type 2 Diabetes

Type 2 diabetes occurs when the body doesn’t use insulin properly, causing blood sugar levels to rise [2]. This is due to the pancreas producing too little insulin and the body’s cells not responding well to it. Over time, high blood sugar can damage the eyes, kidneys, nerves, and heart[2].

Although once known as “adult-onset diabetes,” type 2 can now affect children, largely due to rising obesity rates[2]. While there’s no cure, the condition can often be managed with weight loss, healthy eating, exercise, and, when needed, medications or insulin therapy[2].

Common symptoms may develop gradually and include:

  • Increased thirst and urination

  • Excessive hunger

  • Weight loss

  • Fatigue

  • Blurred vision

  • Slow-healing sores

  • Frequent infections

  • Tingling or numbness in hands/feet

  • Darkened skin patches, especially in the neck or armpits

Leptin, Obesity, and Type 2 Diabetes

Leptin, a hormone produced by fat cells, plays a central role in appetite control, energy balance, and glucose regulation[3]. In a healthy system, leptin levels rise as fat stores increase, signaling the brain to reduce food intake and increase energy expenditure[3].

But in obesity, something goes wrong: leptin levels are high, but the brain becomes resistant to its effects. This leptin resistance means the brain doesn’t register fullness, which contributes to increased food intake and, over time, insulin resistance a key feature of type 2 diabetes (T2DM). Leptin acts through several neuronal pathways, including GABAergic neurons and cells in the ventral premammillary nucleus of the hypothalamus, though the exact locations and mechanisms are still being studied [3].

Why This Matters

This research challenges the idea that obesity is simply the result of overeating or a lack of willpower. Instead, it highlights a deeper issue: neuroinflammation. The food we eat doesn’t just affect our waistline—it changes the way our brain functions. Inflammation in the hypothalamus can alter how we process hunger and fullness, pushing us toward patterns of overeating and disrupted metabolism.

Understanding this connection opens the door to new therapeutic strategies. If we can find ways to reduce brain inflammation or restore leptin sensitivity, we might be able to intervene early in the development of obesity and metabolic disease, not just treat the symptoms after the fact.

[1]Jais A, Brüning JC. Hypothalamic inflammation in obesity and metabolic disease. J Clin Invest. 2017 Jan 3;127(1):24-32. doi: 10.1172/JCI88878. Epub 2017 Jan 3. PMID: 28045396; PMCID: PMC5199695.

[2] Mayo Clinic. (2025, February 27). Type 2 diabetes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193

[3]Manglani, K., Anika, N. N., Patel, D., Jhaveri, S., Avanthika, C., Sudan, S., Alimohamed, Z., & Tiwari, K. (2024). Correlation of Leptin in Patients With Type 2 Diabetes Mellitus. Cureus, 16(4), e57667. https://doi.org/10.7759/cureus.57667

Uncategorized

Pattern Separation in the Dentate Gyrus

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Figure 1. Impact of stress and anxiety on pattern separation.
Created by Sharleen Mtesa. The image shows a brain with disrupted signals and emotional shadows, symbolizing how stress affects memory. Puzzle pieces and swirls represent confusion, while the background figure reflects emotional burden.

Have you ever noticed how certain memories, especially those tied to fear, stress, or strong emotions, seem impossible to forget? These moments, whether terrifying, traumatic, or deeply moving, often stay with us for life. Scientists have found that a small part of the brain called the dentate gyrus (DG) plays a major role in this [1]. The DG, located in the hippocampus, processes incoming information and helps determine which memories are stored long-term, particularly those linked to strong emotions. 

But memory isn’t just about storing emotional experiences, it’s also about keeping them distinct. When stressful or emotional events are similar, how does the brain prevent confusion between them?

Therefore, one key function of the DG is pattern separation, the brain’s ability to transform similar experiences into distinct, non-overlapping memories.

Figure 2. The location of the dentate gyrus in the brain.
This image shows where the dentate gyrus is located inside the hippocampus, a part of the brain involved in memory and emotion.[2]

How the Brain Keeps Stressful Memories Separate

According to the paper “Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways”, the DG achieves pattern separation through a very selective process. Only a small number of neurons in the DG become active during a stressful experience. This phenomenon, called sparse activation[1], helps keep memories sharp and distinct.

But this selectivity isn’t random, it’s carefully controlled by molecular switches within the brain cells. One of the most important switches is a histone tag called H3S10p-K14ac. Think of it like a key that unlocks tightly packed DNA, allowing important memory-related genes, like c-Fos and Egr-1, to be turned on. Without this tag, these genes remain inactive.[1]

Even though stress activates many parts of the brain, only DG neurons with this specific histone tag begin recording the memory. This ensures that the brain focuses its response on just a few key cells, helping to preserve the distinctiveness of each memory.

How the Dentate Gyrus Works Its Memory Magic.

The DG has some cool tricks to keep your memories sharp and organized:

1. Sparse Coding
  • Only a small group of neurons fire for each experience.
  • ➡️ Prevents similar memories from overlapping.
  • Example: Meeting two people with similar voices? DG helps you tell them apart.
2. Input from the Entorhinal Cortex (EC)
  • EC sends sensory + spatial data to the DG.
  • DG reshapes it and passes it to the hippocampus.
  • Ensures detailed, clear memory storage.
3. Inhibitory Microcircuits
  • GABAergic interneurons = your brain’s memory traffic cops.
  • Prevents too many neurons from firing at once.
  • Example: Helps you remember where you actually parked today, not yesterday.
4. Neurogenesis = Fresh Memory Power
  • DG keeps growing new neurons, even in adulthood.
  • These newbies help make fresh, flexible, and distinct memories.
  • Keeps your brain adaptable, not stuck in the past.

Figure 3. Simplified Flow of Information in the Hippocampal Formation.
This figure shows how sensory input from cortical association areas is processed by the parahippocampal and perirhinal cortices, then transmitted to the entorhinal cortex, which relays it to the hippocampus. Within the hippocampus, the dentate gyrus (DG) acts as the initial processing stage, playing a key role in pattern separation, transforming similar inputs into distinct memory representations before passing information to CA3, CA1, and the subiculum. [3]

How Stress & Anxiety Mess With the DG’s Memory Magic.

Stress doesn’t just make you feel awful, it actually affects how your brain remembers.

  1. Stress Hurts Neurogenesis
  • DG produces new brain cells throughout life (neurogenesis).
  • Chronic stress = high cortisol (a hormone the body releases under stress) = fewer new neurons. [4]
  • Fewer neurons → DG can’t keep memories separate → confusion & memory blending.
     2. HPA Axis Overdrive Weakens DG
  • When stress continues for too long, the HPA axis(the body’s stress response system) stays overactive, keeping stress hormones high. [5]
  • High cortisol levels weaken connections between neurons in the DG.
  • ➡️ This makes it harder for the brain to separate new experiences from past ones
  • Leads to anxiety, fear, and biased memory recall.
  1. Pattern Completion Takes Over
  • DG usually favors pattern separation.
  • Under stress, it shifts to pattern completion (retrieving old memories based on partial cues).
  • What that looks like:
    • Fear Overgeneralization: Mistaking safe situations for dangerous ones.
    • Exaggerated Emotional Reactions: Past trauma colors present experiences.
  1. Memory Interference: Past vs. Present
  • DG normally prevents interference between old and new memories.
  • Stress disrupts that filter:
    • Past memories bleed into new ones.
    • Makes it hard to feel safe even when you are. [6]

How to Boost DG Function & Beat Stress

Want to keep your DG happy and your memories sharp? Try these:

  • Exercise: Boosts neurogenesis + lowers cortisol
  • Mindfulness & Meditation: Calms your stress response system
  • Cognitive Behavioral Therapy (CBT): Helps reframe overgeneralized fears
  • SSRIs/Antidepressants: Improve memory-related brain plasticity

Final Thoughts: Protecting Your Brain’s Memory Filter

The dentate gyrus may be small, but its role in shaping how we process and separate emotional memories is huge. When working well, it helps us distinguish the past from the present, keeping our memories organized and our reactions in check.

But chronic stress and anxiety can disrupt this process, blurring lines between memories, fueling fear, and making it harder to feel safe in the moment. The good news? The DG is flexible and responsive. With habits like exercise, mindfulness, therapy, and proper treatment, we can support brain health and improve memory clarity.

Because memory isn’t just about holding on, it’s about understanding, adapting, and moving forward. 





 

 

 

 

 

Footnotes:

[1] Reul J. M. (2014). Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways. Frontiers in psychiatry, 5, 5. https://doi.org/10.3389/fpsyt.2014.00005

[2] Centre of Excellence for Early Childhood Development. (2008, December 5). Glossary – Brain. Encyclopedia on Early Childhood Development. https://www.child-encyclopedia.com/sites/default/files/docs/glossaire/Glossary_Brain_DG.pdf

[3] Weilbächer, R., & Gluth, S. (2016). The interplay of hippocampus and ventromedial prefrontal cortex in memory-based decision making. Brain Sciences, 7(1), 4. https://doi.org/10.3390/brainsci7010004 

[4] Schoenfeld, T. J., & Gould, E. (2012). Stress, stress hormones, and adult neurogenesis. Experimental neurology, 233(1), 12–21. https://doi.org/10.1016/j.expneurol.2011.01.008

[5] Lee, J. W., & Jung, M. W. (2017). Separation or binding? Role of the dentate gyrus in hippocampal mnemonic processing. Neuroscience & Biobehavioral Reviews, 75, 183-194. https://doi.org/10.1016/j.neubiorev.2017.01.049 

[6] Kim, E. J., Pellman, B., & Kim, J. J. (2015). Stress effects on the hippocampus: a critical review. Learning & memory (Cold Spring Harbor, N.Y.), 22(9), 411–416. https://doi.org/10.1101/lm.037291.114 



Disease/Health

Protecting Your Brain to Protect Your Body: A New Angle on Preventing Obesity

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Abstract created by Gabe Sparks

Obesity is often labeled as a simple imbalance between the calories we consume and the calories we burn, but this disease runs much deeper than public perception suggests. It’s not just about food intake; it’s also about complex processes happening within the brain. Recent research shows that inflammation in certain brain regions can disrupt normal signaling in neural pathways, contributing to the development of obesity.1

One of the most affected areas is the hypothalamus, a region that plays a critical role in regulating feeding behavior and energy expenditure.1 For our bodies to maintain a healthy balance between the energy we take in through food and the energy we burn through physical activity the hypothalamus needs to function properly. When this region becomes inflamed, the signaling from key hormones like insulin and leptin can become impaired. These disruptions confuse the body’s internal cues for hunger and energy use, setting the stage for weight gain and metabolic dysfunction.

This is just a brief look at how obesity is far more complex than many realize. The story goes beyond diet and exercise. It reaches into the brain itself, revealing layers of complexity we’re only beginning to understand.

Understanding the Science

To understand the background of this metabolic disease, there are two key scientific areas to focus on: the specific neurons responsible for regulating energy balance, and the pathways disrupted by inflammation that lead to dysfunction in this system.

The two main types of neurons involved in energy homeostasis are AgRP (Agouti-related peptide) and POMC (pro-opiomelanocortin) neurons.1 Both are located in the arcuate nucleus (ARC) of the hypothalamus and play crucial, but opposite, roles in managing food intake and energy expenditure. When functioning properly, as shown on the left side of Figure 1, these neurons maintain a healthy balance between energy coming in and energy being used.

Figure 1.Diagram illustrating the neurons involved in metabolic homeostasis and the disruptions seen in obesity and metabolic syndrome.

However, in obesity and metabolic syndrome, this balance is disrupted. Overactivation of AgRP neurons results in increased signaling to the paraventricular nucleus (PVN), leading to reduced energy expenditure and increased food intake.1 This dysregulation is one of the earliest signs of hypothalamic inflammation and is a driving force in the development of metabolic disease.

A deeper look into the molecular level reveals how this disruption happens. In a healthy brain, hormones like insulin and leptin bind to their receptors on hypothalamic neurons to help regulate appetite and metabolism. Insulin works by suppressing the activity of a protein called FOXO1, which promotes POMC expression (appetite-suppressing) and reduces AgRP/NPY expression (appetite-stimulating). Leptin activates STAT3, which similarly boosts POMC while suppressing AgRP/NPY activity.1

But in states of chronic inflammation, often triggered by molecules like TNF-α or saturated fats, these hormonal pathways are disrupted. TNF-α activates proteins such as JNK and NF-κB, which interfere with normal insulin signaling.1 This reduces the brain’s sensitivity to both insulin and leptin, weakening their ability to regulate hunger and metabolism. Additionally, inflammation increases the expression of SOCS3, a molecule that further blocks insulin and leptin signaling, reinforcing resistance. The result is a system that no longer responds appropriately to signals of satiety and energy balance, leading to overeating and metabolic dysfunction. These different pathways can be found in Figure 2.1

Figure 2. Diagram depicting the molecular pathways of metabolic inflammation in the hypothalamus.

The Start of Inflammation: Diet, Stress, and Modern Life

Inflammation is typically seen as a natural response to injury or infection, but chronic inflammation, especially in the brain, can be harmful. Today’s modern lifestyle, particularly our diet and stress levels, often acts as a continuous trigger, keeping our immune system in a low-grade, overactive state.2 This persistent inflammation contributes to the disruptions in neural pathways that lead to metabolic diseases.

The American environment plays a significant role in the rise of these conditions. Over time, we’ve witnessed a dramatic shift in the standard diet, marked by excessive consumption of saturated fats, refined carbohydrates, and trans fats, while nutrient-dense foods have become less common. The decline in dietary quality isn’t the only factor at play, though. The increasing presence of stress in our daily lives is another major contributor. The modern world constantly activates the HPA axis, releasing stress hormones like norepinephrine and cortisol.2 Stressors such as academic pressures, financial anxiety, or information overload have led to the prolonged production of pro-inflammatory cytokines, while simultaneously reducing the body’s ability to properly shut off the inflammatory response.

As a result, the combination of poor dietary habits and chronic stress has created an environment that fosters persistent inflammation, which ultimately disrupts the brain’s ability to regulate metabolism and appetite effectively.2

Here is a link to an article that further explores chronic inflammatory diseases and our current lifestyle.

Conclusion: Rethinking Obesity and Metabolic Health

The rise in obesity and metabolic diseases is far more complex than the public’s general understanding. As we’ve discussed, hypothalamic inflammation plays a pivotal role in the disruption of critical neurological pathways that regulate both hunger and energy expenditure. The modern American lifestyle provides an ideal environment for this inflammation, contributing to the growing prevalence of metabolic disorders.

By diving deeper into the mechanisms behind these diseases, we can shift public perception and broaden our approach to addressing them. Tackling the root causes of brain inflammation such as improving nutrition, managing stress, and making healthier lifestyle choices is crucial for long-term change. While the path forward may require significant effort, it’s a challenge we, as a society, must take on to build a healthier future for all.

References

(1)          Jais, A.; Brüning, J. C. Hypothalamic Inflammation in Obesity and Metabolic Disease. Journal of Clinical Investigation 2017, 127 (1), 24–32. https://doi.org/10.1172/JCI88878.

(2)          Bosma-Den Boer, M. M.; Van Wetten, M. L.; Pruimboom, L. Chronic Inflammatory Diseases Are Stimulated by Current Lifestyle: How Diet, Stress Levels and Medication Prevent Our Body from Recovering. Nutrition and Metabolism. 2012. https://doi.org/10.1186/1743-7075-9-32.

Disease/Health

Brain-Body Connection in Obesity

Posted on by hdahlsei / 0 Comment

Recently, hypothalamic inflammation has been linked to obesity. The evidence suggests a high fat diet leads to brain inflammation, causing the uncoupling of food intake and energy expenditure, which leads to overeating and obesity [1].

Normal Metabolic Feedback Loop

In healthy brains, the hypothalamus regulates energy and metabolism successfully. Insulin and leptin anorexigenic (“don’t eat”) signals are proportionate to fat cell mass. This means the brain tells the body to only eat what it needs based on how much energy it has spent [1]. 

More specifically, AgRP neurons are inhibited. These are the neurons telling the body to eat more. Additionally, POMC neurons are stimulated, which sends a “don’t eat” signal to the body. When this is working under normal circumstances, there is a balance between food intake and energy expenditure [1].

Metabolic Feedback Loop [1]
Obesity and Metabolic Syndrome

However, when a high fat diet (especially saturated fatty acids) causes hypothalamic inflammation (specifically due to increased JNK and IKK inflammatory mediators), a couple things happen. There is resistance to insulin and leptin signaling. Which essentially means the brain is not listening to these signals. Also, food intake and energy expenditure is uncoupled. This means the same metabolic feedback loop described above doesn’t work right [1].

AgRP neurons are not inhibited, causing too much excitatory (“eat”) signalling. Additionally, POMC neurons are not stimulated, causing not enough inhibitory (“don’t eat”) signalling. This means the brain tells the body to eat, regardless of how much energy is spent, or how much fat cell mass there is. The body eats too much relative to how much energy is spent, making these processes uncoupled and unbalanced [1].

Long Term Effects

The immediate effects of a high fat diet and brain inflammation described above are dysregulating, but there are also impacts with a long term high fat diet. 

  • Alteration in synaptic plasticity for hypothalamic neuronal systems
  • Apoptosis of hypothalamic neurons and reduction of synaptic inputs
  • Increased microglia in the hypothalamus, causing more inflammation
  • Increased astrocytes in the hypothalamus, causing more inflammation
  • Impacts on the blood-brain-barrier’s integrity
  • Places in the brain and body that the hypothalamus projects to are also impacted. This includes: the rostral ventrolateral medulla, NTS, and dorsal motor nucleus of the vagus nerve in the hindbrain [1].

Interoception

So, in obesity, the signals between the brain and body are off balance, causing overeating and obesity. Interestingly, there is another cause for brain and body disconnect that could potentially lead to overeating and obesity as well. In this instance, it is not inflammation that causes obesity, but a lack of interoception ability. Interoception is:

  • The perception of internal signals from the body [2]
  • The ability to sense, interpret, and integrate signals originating from within the body [3]
  • Signals from internal organs to the brain
  • The ability to keep the body in balance
  • Examples include being able to feel: hunger, thirst, cold, warm, tired, racing heart… 

The main way the brain is connected to the body in order to send these signals is the vagus nerve. It is a major brain-body communication pathway, and has sensory neurons that innervate internal organs [3]. 

Deficits in Interoception

Some people are better at sensing these brain-body communication signals than others. One way this is measured is a task to count your heartbeat without using your fingers to find your pulse. People who have worse interoception are those with autism, ADHD, eating disorders, and depression [2].

Interoception and Obesity

Deficits in interoception are associated with relying less on hunger and satiety signals to determine when to eat. Deficits in interoception are also linked with a higher BMI. However, scientists studying this are unsure of the direction or causality of the issue. Meaning, does interoceptive deficits cause increased BMI, or are interoception deficits a result of an increased BMI? [4]

So, we know a high fat diet, leading to inflammation, causes obesity. But we also know deficits in interoception are linked to obesity. It is important to understand these links to obesity in order to make the healthiest choices for your own brain and body.

References

[1] Jais, A., & Brüning, J. C. (2017). Hypothalamic inflammation in obesity and metabolic disease. Journal of Clinical Investigation, 127(1), 24–32. https://doi.org/10.1172/jci88878 

[2] McDonough, M. (2024, June). Making Sense of Interoception. Harvard Medicine Magazine. https://magazine.hms.harvard.edu/articles/making-sense-interoception 

[3] Robinson, E., Foote, G., Smith, J., Higgs, S., & Jones, A. (2021). Interoception and obesity: A systematic review and meta-analysis of the relationship between interoception and BMI. International Journal of Obesity, 45(12), 2515–2526. https://doi.org/10.1038/s41366-021-00950-y 

[4] Robinson, E., Marty, L., Higgs, S., & Jones, A. (2021). Interoception, eating behaviour and body weight. Physiology & Behavior, 237. https://doi.org/10.1016/j.physbeh.2021.113434

Uncategorized

The U.S. Diet’s Impact on High Obesity Rates

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Obesity is common in the United States, with more than 1 in 5 people in the United States being obese. [1] The figure below represents that some areas of the U.S., such as the Midwest and the South, have even higher rates of obesity.

Figure 1: Obesity prevalence in the United States in 2023 [2]
United States has one of the highest rates of obesity, but it is a problem in other areas of the world as well. The map below portrays the rates of obesity across the world in 2016.

Figure 2: Global rates of people who are overweight or obese in 2016 [3]
Yet, what do we know scientifically about obesity and Metabolic Syndrome? Each area in the world has a different diet, so how does the food commonly eaten in the United States contribute to the high prevalence of obesity?

What’s Happening in the Body During Obesity

The hypothalamus, a region in the brain, is responsible for our appetite and eating behaviors. There are AgRP neurons and POMC neurons inside the hypothalamus. The AgRP neuron signals tells us we’re not full, while POMC neuronal signals tells us we’re full. The yellow AgRP neurons will activate the blue MC4R neurons, the “eat” neurons so we keep eating, while the POMC neurons will inhibit the MC4R. In other words, the POMC will make sure the “eat” neuron, the MC4R neurons, will stop telling us to eat.

Figure 3: Neurons related to full or hungry feelings [4]
However, in obesity and metabolic syndrome, this process goes out of balance. The AgRP neurons will continue activating the eat neurons, and the POMC neurons won’t tell us we’re full, so we end up eating more than we should because we don’t feel full.

Impact of a High Fat Diet on our Bodily Processes

Obesity also causes low-grade inflammation throughout the body that can disrupt important processes, including neurons such as AgRP and POMC. Some of this inflammation can arise from a high fat diet, even within a few days after a high fat diet. This diet can cause acute inflammation in the hypothalamus. [5] Chronic consumption of a high fat diet will perpetuate the inability to feel full when you’re supposed to.

A high fat diet is when 30-60% of calories consumed are from unsaturated and saturated fats. [6]

Chart of good and bad fats [7]
Saturated fats trigger inflammatory pathways, and decrease insulin and leptin sensitivity, something that helps us break down food into nutrients. Meanwhile, unsaturated fats help increase insulin and leptin sensitivity which helps us break down our food into their nutrients. [8] Saturated fats are harmful in large amounts; unsaturated fats are helpful!

A Reflection on Common U.S. Foods

Considering that foods that are high in saturated fats such as fried food, red meat, chips, vegetable oil, and dairy products are in the everyday diet for a lot of Americans, it’s no wonder the obesity rate is so high in the U.S. compared to other countries. Especially considering our large portion sizes that encourage over-eating.

Food is not the enemy, neither is saturated fats in low amounts, but it’s important to have balance in our diets to ensure a healthy life. A hamburger and fries won’t completely harm your body, but it’s beneficial to limit the consumption of these “bad” foods and balance it with healthy foods.

 

References 

[1,2] CDC. (2024, September 12) Adult Obesity Prevalence Maps.  https://www.cdc.gov/obesity/data-and-statistics/adult-obesity-prevalence-maps.html

[3] Ritchie, H., Roser, M. (2017, August) Obesity. Our World in Data. https://ourworldindata.org/obesity

[4,5] Jais, A., Brüning, J. C., (2017). Hypothalamic inflammation in obesity
and metabolic disease. The Journal of Clinical Investigation, Vol. 127(1): 24-32. doi:10.1172/JCI88878.

[6] Willebrords, J, et. al. (2015). Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research. Progress in Lipids Research, Vol. 59: 106-125. https://doi.org/10.1016/j.plipres.2015.05.002

[7] YMCA. (2022, June 1). Four Myths About Eating Fats. https://lafayettefamilyymca.org/myths-about-eating-fats-2/

[8] Jais, A., Brüning, J. C., (2017). Hypothalamic inflammation in obesity
and metabolic disease. The Journal of Clinical Investigation, Vol. 127(1): 24-32. doi:10.1172/JCI88878.

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