First marketed in the 1970’s by the Clinton Corn Processing Company and reaching peak usage in the late 1990’s, High fructose corn syrup (HFCS), a sweetener made from corn, became a godsend to corporations such as Coca-Cola, Kellogg’s, Nabisco, Capri, Ocean Spray, Starbucks, Heinz, Yoplait, Ben & Jerry’s, Dreyer’s, and hundreds more. No longer did they have to rely heavily on costly sugar (Sucrose) imports from Mexico and the rest of South America, now they could get tap the never ending stream of US corn as a sugar source. HFCS comes in two primary compositions—HFCS-42 and HFCS-55. This means it is composed of either 42 percent or 55 percent fructose, with the remaining sugars being glucose. Similar to sucrose in monosaccharide composition, HFCS monosaccharide units are not bonded together, which results in a liquid sugar instead of crystalline. This characteristic is particularly significant because it allows the transportation of larger quantities, more precise control during alcoholic fermentation, and most importantly, allows the adjustment of the glucose to fructose proportion in HFCS.
For the sake of providing context, here are a few statistics on HFCS consumption. According to Duke Health, 52 percent of adults consume between one and six sugary beverages per week, which are a primary source of high-fructose corn syrup in the average diet. The same source also estimates that about one-third of adults admit to having at least one sugary drink each day. According to Consumer Reports Organization, there was a 1,000 percent increase in the consumption of high-fructose corn syrup between 1970(introduction of HFCS) and 1990(peak usage of HFCS). In 2009, the average American consumed about 35.7 pounds of high-fructose corn syrup, while reports the Illinois Farm Bureau. Simply said, the ubiquitous composition of HFCS in typical diet of the average American is staggering!
Transitioning to the CNS’s role in energy metabolism, the schematic below shows arcuate nucleus (ARC), a region of the hypothalamus that contains neurons sensitive to insulin and leptin, hormones that regulate energy homeostasis.
Neurons in the ARC that contain neuropeptide Y (NPY), agouti-related protein (AGRP), and gamma-amino butyric acid (GABA) increase appetite; while neurons that contain pro-opiomelanocortin (POMC), alpha-melanocyte stimulating hormone, beta-endorphin, acetylcholine, and cocaine-and-amphetamine-regulating transcript (CART) decrease appetite. When circulating in the blood, insulin, leptin, and ghrelin modulate both the anorexigenic and orexigenic neurons, in addition to the higher order neurons too. One can imagine this hormonal control of energy homeostasis to be like see-saw action between food intake and food expenditure, effected by NPY/AGRP and POMC neurons. One interesting point to make is that the blood brain barrier in the ARC is relatively less developed, so more permeable, hence it allows agonist and antagonistic species into the ARC. This results in signal initiation and propagation when those substances bind to receptors on the many neurons. The ease of permeability also presents an opportunity for intranasal administration of therapeutic agents.
So what really is the big deal with HFCS? After all, regular sugar contains both glucose and fructose… you might be wondering. Well, both HFCS and sucrose are empty calories, they have hardly any nutritional value and our bodies get all the sugar it needs from a regular nutritional meal anyway. The real issue with HFCS lies in its metabolism to prepare for entrance into the Citric Acid Cycle. Below is a diagram of glycolysis. Major regulatory points of glucose homeostasis are steps 1, 3, and 10. Fructose enters glycolysis as shown in the diagram below. It bypasses the regulation at step 3, and is metabolized as fatty acids would be. This results in high blood sugar levels, disrupts the balance in the control of NPY/AGRP and POMC neurons, leading to weight gain, as the extra sugar becomes stored as fat. Subsisting on a diet high in HFCS results in increased hunger due to an insufficient supply of nutrients present in such foods. This then leads to over nutrition, which leads to weight gain and hyperinsulinemia. Oxidative stress, and endoplasmic reticulum stress then results in hypothalamic neurons, resulting in protein misfolding and inflammation through the NFkB pathway, the latter of which leads to apoptosis of neurons in the hypothalamus concerned with energy metabolism. Insulin resistance (type II diabetes) then results. Thanks HFCS – Yours truly!
Correlating High Fructose Corn Syrup Consumption With CNS Insulin Signaling and Obesity.
