神经生物学 15、 夏8 下丘脑与食欲控制.pptVIP

* Rond 30 jaar AT8 PVN 28 % SMALLER,38% LESS CELLS, 42% LESS OXT CCELLS * 下丘脑与食欲控制 浙江大学医学院 神经生物学系 + - One of the most important adipose derived protein hormone, 16 kDa, regulating energy intake and expenditure, including appetite and metabolism. The Ob(Lep) gene is located on chromosome 7 in human. Mutant obese mice (1950): massively obese and excessively voracious. Two classes: ‘ob/ob’ - mutations in the gene for leptin, and ‘db/db’ - mutations in the gene that encodes the receptor for leptin. When ob/ob mice are treated with of leptin (injection), they lose the excess fat and return to normal body weight. Leptin (Greek leptos meaning thin) a mouse unable to produce leptin thus resulting in obesity (left) and a normal mouse (right) Leptin: discovered in 1994 by Jeffrey M. Friedman et al, Rockefeller University. Leptin acts in the hypothalamus inhibiting appetite by (1) counteracting the effects of neuropeptide Y; (2) counteracting the effects of anandamide (a potent feeding stimulant,一种内源性大麻素， “极乐酰胺”) (3) promoting the synthesis of alpha-MSH (an appetite suppressant). This inhibition is long-term. Leptin (Greek leptos meaning thin) Pathogenesis of obesity: 3 general ways that Leptin alterations lead to obesity. a, Failure to produce leptin; b, inappropriately low leptin secretion for a given fat mass, in which the fat mass would expand until ‘normal’ leptin levels are reached, c, relative or absolute insensitivity to leptin, associated with increased circulating leptin. In general, high plasma leptin levels are evident in obese rodents and humans. In a subset of cases, obesity is associated with normal levels of leptin. Leptin binds to NPY neurons in the ARC and decreases NPY activity. Leptin signals to the brain that the body has had enough to eat, producing a feeling of satiety. A very small group of humans possess homozygous mutations for the leptin gene a constant desire for food, severe obesity, treated somewhat