Neurobiological Mechanisms

Flier summarizes the many possible pathophysiological mechanisms involved in the development and maintenance of obesity.

This field of research has been almost unattainable until leptin was discovered in 1994.

Since this discovery, many other hormonal mechanisms involved in regulating appetite and food consumption patterns in storage in adipose tissue and the development of insulin resistance, have been elucidated.

Since the discovery of leptin, the grelina, orexins, PYY 3-36, and many other mediators have been studied. Adipoquinas are the mediators produced by adipose tissue, is thought to modify their actions and many obesity-related diseases.

The leptin grelina and are seen as complementary in their influence on appetite, grelina produced by the stomach, modulate the control of appetite in the short term (to eat when the stomach is empty and to stop when your stomach is full).

Leptin is produced by adipose tissue to signal fat reserves stored in the body and mediate the control of appetite in the long term (to eat more when fat reserves are low and less of the fat reserves are high).

Although the administration of leptin may be effective in a small group of obese subjects who are leptin deficient, most obese individuals appear to be more resistant to leptin. This resistance explains in part why administration of leptin has not been shown to be effective in suppressing the appetite in most obese subjects.

While leptin and grelina are produced peripherally, they control the appetite through their actions on central nervous system. In particular, these and other appetite-related hormones act on the hypothalamus, a brain region central to the regulation of food consumption and energy expenditure.

There are several groups within the hypothalamus that contribute to this role integration of appetite, being the path of melanocortin better understood. The tour begins as an area of the hypothalamus, the nucleus arcuate, which has outputs to the lateral hypothalamus ( LH) and ventromedial (HVM), centers of food and satiety in the brain, respectively.

The Arcuate core contains two distinct groups of neurons. The first group co-express neuropeptide Y (NPY) and agouti related peptide (AgRP) and receives stimulatory signals from the lateral hypothalamus and inhibitory signals from the ventromedial hypothalamus.

The second group co-express proopiomelanocortin receives stimulatory signals from the ventromedial hypothalamus and inhibitory signals from the lateral hypothalamus.

Consequently, neurons NPY / AgRP stimulate satiety and inhibit feeding, whereas neuronasPOMC / CART stimulates satiety and inhibit feeding. Both groups of neurons in the nucleus arcuato are partly regulated by leptin. Leptin inhibits NPY group / AgRP, while stimulating group POMC / CART. Therefore a deficiency in leptin signaling, via leptin deficiency or leptin resistance, leads to overfeeding and may account for some forms of genetic and acquired obesity.