The 7 Keys to Permanent Weight Control

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How do Leptin and Ghrelin Work in the Hypothalamus?

In the center of the brain is a small collection of cells called the hypothalamus. It is further divided up into sections, one of which is called the arcuate nucleus. In this section of the brain two cell types control hunger, satiety and metabolic rate. The first of these cells is called the NPY/AGRP (Neuropeptide Y/Agouti Related Protein) cell. It can be thought of as the hunger cell. When stimulated it release two chemicals, NPY and AGRP. NPY travels to other parts of the hypothalamus where it shuts down metabolic rate and increases cravings for carbohydrates. AGRP works to block the output from the other cell in arcuate nucleus called the POMC (proopiomelanocortin) cell. This cell is the satiety cell. When it is activated it releases a chemical called alpha MSH (melanocyte stimulating hormone). Alpha MSH binds to the MC4 (melanocortin 4) receptor and increases metabolic rate and promotes a satiated feeling. AGRP blocks alpha MSH from binding to the MC4 receptor.

In addition when the NPY/AGRP cell is activated it has direct neural connections with the POMC cell. These connections use a chemical called GABA (gamma amino butyric acid) to allow the NPY/AGRP cell to directly inactivate the POMC cell.

There are many hormones that modulate the activity of the NPY/AGRP and the POMC cell. The two major hormones that effect these critically important cells are leptin and ghrelin. Ghrelin turns on the NPY/AGRP (hunger) cell and turns off the POMC (satiety) cell and leptin does just the opposite. In addition there are many hormones and chemicals that modulate how ghrelin and leptin effect these cells.

Some of these chemicals stimulate ghrelin's and inhibit leptin's activity in the arcuate nucleus. These can be thought of as hunger promoters. The main hunger promoter is called the CB1 receptor (cannabinoid receptor 1). The CB1 receptor is activated by cannabinoids. We have natural cannabinoids called endocannabinoids and we can get cannabinoids from outside the body. Marijuana's active ingredient is THC (tetrahydrocannabinoid). It binds to the CB1 receptor and increases hunger. Thus the munchies with smoking pot. While chocolate doesn't have any cannabinoids in it, it does have chemicals that are very similar to a natural occuring cannabinoind called anandamide. These chemicals in chocolate prevent the natural degradation of anandamide and thus increase its level which again stimulates the CB1 receptor and makes us hungrier.

We also have many chemicals and hormones that turn the hunger cell off and the satiety cell on. One of these is a hormone produced by the intestines called oxyntomodulin. When food arrives in the small intestine, it releases oxyntomodulin. The oxyntomodulin travels to the brain where it prevents ghrelin from stimulating the NPY/AGRP cell. The small intestines also make another hormone in response to protein being delivered to the small intestine called PYY (peptide YY). PYY travels to the brain where it promotes leptins ability to stimulate the satiety cell. When the pancreas senses fat in the intestines it releases a hormone called CCK (cholecystokinin). CCK travels to the brain where it prevents ghrelin from turning off the satiety cell. Thus oxyntomodulin, PYY and CCK are all satiety hormones that effect the biochemistry of ghrelin and leptin in the hypothalamus.

      Copyright 2005, Infinity Medical Systems, Inc.