Hormonal Control of Appetite/Hunger/Satiety

As the science progresses, there may be new hormones added to the list—and potentially, some may be more critical as we learn of their role in controlling appetite. For now, here is a description of the most important active hormones(2) in appetite control.

Leptin: Leptin sends the signal of “I have no appetite” to the brain and brainstem. It is primarily made by adipose (fat) cells, with some produced by intestinal cells. Leptin inhibits hunger by acting on cells found in various regions of the brain including the hypothalamus—that is why it is often called the “satiety hormone”. Its primary role is to regulate fat cell storage, but leptin can also affect the immune system, new vascular growth, both male and female fertility, male and female puberty, and bone mass.

Perhaps confusingly, leptin levels tend to be high in obese individuals and lower in thin individuals. Obese individuals are considered to be leptin resistant—this is similar to the insulin resistance seen in pre-diabetes and diabetes. Leptin resistance indicates that the cells of the body have lost the responsiveness to leptin—in obesity, the fat cells keep on making leptin, but the brain cells don’t seem to respond by decreasing hunger. Leptin resistance results in constant hunger and increased food intake—usually leading to MORE weight gain and MORE adipocytes producing MORE leptin—it becomes a sort of vicious weight-gain cycle. This scenario may also explain why diets—especially demanding diets—don’t work for the long term. Leptin resistance combined with behavioral reactions seems to make it all seem impossible!

In thin or normal weight people, leptin levels tend to be directly based on the amount of fat cells in the body—and thin or normal weight people tend to be sensitive to the levels of leptin produced by the fat cells, resulting in more appropriate hunger signals.

Ghrelin is produced by the stomach, with some synthesized by the pancreas, small intestine, and brain. Ghrelin is called the “hunger hormone” because it stimulates appetite, food intake, and the growth of fat storage. It acts on the hypothalamus but also appears to act in the brain’s reward processing—further enhancing food intake. Ghrelin(3) production is regulated by meal routines and food intake—ghrelin levels increase when hungry or during times of fasting and decrease by eating. Ghrelin is also involved in insulin secretion and the control of blood sugar levels.

Cholecystokinin, or CCK, is produced by the small intestine and increases the release of digestive enzymes. However, it also acts as an appetite suppressant by binding to cells in various areas of the brain. CCK is released at especially high levels when you eat a fatty meal—this may be why eating fatty meals is often seen as a pleasant experience—by activating reward centers in the brain. CCK(4) can also slow down digesting, increasing the sense of feeling full.

Adiponectin is involved in regulating blood sugar levels and in the breakdown of fatty acids. It is made by adipocytes—and the human placenta. Adiponectin(5) can increase insulin sensitivity and can act in concert with leptin, including increasing weight loss.

Glucagon-like peptide-1, or GLP-1, is produced by cells in the small intestine and by neurons within the brainstem. Most effects of GLP-1 may be particularly important in diabetes because it can promote the secretion of insulin and helps support the body’s synthesis of insulin by the pancreatic beta cells. It also promotes satiety or the sense of having had enough to eat. Finally (well, again for now…), GLP-1(6) reduces appetite by slowing down digestion.