Can genetics affect obesity and the brain?

There are many negative side effects of being obese. Some of the effects that are not looked at though, are the effects that obesity has on the brain. There are many problems that can occur within neurotransmitters because of high fat diets and obesity. One of the main systems that is affected by a high fat diet is that leptin activity is inhibited. This causes many downstream effects to occur. One of these is that Erk is inhibited and this causes the up regulation of the Gsk-3 pathway. This is detrimental because less BDNF is produce. BDNF is a transcription factor that helps protect the cells and prevent apoptosis. A high fat diet will also increase the chances of having type II diabetes. With type II diabetes there will be insulin resistance within the cell. From one of my previous blogs, it can be seen that insulin resistance will lead to decreased cognitive function. This insulin resistance will also cause the inhibition of leptin activity. Then the cycle that was described earlier will occur in the neurons. Another result from a high fat diet is lipid peroxidation. This causes oxidative stress to occur within the cell. This oxidative stress will disrupt the unfolded protein response (UPR). If the UPR is not correctly working, the cell will end up dying because of apoptosis. This apoptosis will cause a decrease in cognitive function. Another problem that can result from this diet type is disruption in the blood brain barrier. The blood brain barrier is disrupted because of the down regulating the mRNA expression of Claudin-5 and -12. The reason that this is a problem is that harmful chemicals can enter into the brain if the blood brain barrier is not working correctly. It also disrupts the ability of the brain to flush molecules out of the system.
One important idea that is associated with the problem is that some people may have a gene that may incline them to be more obese. This gene is known as the fat mass and obesity associated gene (FTO). The gene is for a enzyme that catalyzes the demethylation of 3-methylthymine. This gene has been shown to be upregulated after food deprivation and negatively correlated with the food stimulation of food intake. This gene has been shown to have a greater effect on the person if they have both alleles for it. This means that if both of the chromosomes have the FTO gene, the person has a higher chance of being obese. The problem with this though is that people may try to use this as an excuse on why they are obese. This gene may cause this but it can have no effect if someone diets and exercises properly. Another problem with this gene is that people with it tend to have a tendency to show more symptoms that are commonly associated with metabolic syndrome. These symptoms include higher fasting insulin, glucose, and triglycerides, and lower HDL cholesterol. This may be caused though by the weight gain rather than the gene itself. A final problem that may occur because of this gene is that there is a decrease in the frontal lobe in the brain and an impaired verbal fluency performance. Like I stated earlier, a person may have this gene but it can be a non-factor if some has the proper diet and exercise regimen.