6. Hormones and Enzymes that Control Appetite

The fat cells are able to influence the muscles to preferentially take up fats rather than glucose by releasing certain hormones into the blood, hormones that also have a powerful influence over appetite. One of these hormones is leptin. While leptin influences the muscle cells indirectly through its signaling in the hypothalamus, it also stimulates the muscle cells directly, and influences them to oxidize fatty acids in their mitochondria [26]. Leptin also encourages the fat cells to release their fats through lipolysis [24]. All of these actions work in concert to redirect fuel usage away from glucose. The programming of the muscles to preferentially consume fats aligns well with the fat cells' infusion of fats into the blood and absorption of sugars through their fat-producing factories.

Leptin also has the effect, via the hypothalamus and pituitary gland, of suppressing appetite. Adiponectin is another hormone released by fat cells, and it is generally agreed that adiponectin induces hunger. Leptin and adiponectin levels would ordinarily fluctuate throughout the day, with leptin levels rising at night to encourage a switch from glucose-based to fat-based energy management. However, in the obese person, the leptin levels are typically high all the time, and the adiponectin levels are kept very low [41]. High levels of leptin in the blood signal to the appetite center in the brain a sense of being full [8], whereas high levels of adiponectin are hunger-inducing. This means that the obese are being informed both that they are full, and that they are not hungry. You would think that this would protect them from overeating. However, it is likely that the observed insensitivity to leptin as an appetite suppressant in the obese is also related to calcium depletion, because the signaling mechanisms that respond to leptin in both the hypothalamus (Details) and the pituitary gland (Details) depend on changes in internal calcium concentrations.

So, why does the obese person overeat? I have reached the almost inescapable conclusion that the culprit is over-sensitized AMPK, as is also suggested by several other researchers [15][17][18]. AMPK operates not only in muscle cells, but in just about all cells of the body [15]. In particular, it plays a critical role in sensors in specialized cells in the brain: in the hypothalamus and the pituitary gland. These cells release chemicals into the blood that influence the liver, the pancreas, and the appetite, in terms of turning on or turning off mechanisms that will provide further fuel into the system, in the form of either fats or glucose.

As was said before, whenever the muscles exert themselves for sustained periods, they soon reach a critical point where large amounts of ATP have been converted to AMP, in the process of releasing energy to drive muscle contraction. The AMP:ATP ratio rises sharply. This activates AMPK, which then reprograms the muscle to both increase the levels of calcium inside the cell and consume more sugar [30][32][37], a very bad idea since calcium and insulin are in short supply. Certain GI or "Glucose Inhibited" cells in the hypothalamus, as well as alpha cells in the pancreas, are programmed to respond to low glucose levels by instructing the liver to release more sugars and increasing the appetite for foods with a high glycemic index. They essentially broadcast the urgent message to the brain that more glucose is desperately needed. The person is compelled to consume sugars and carbs that will digest very quickly and further raise the already high blood sugar levels.