陕西

河南

河北

山东

httpd.conf

lilo.conf

inetd.conf

resolv.conf

河南

河北

内蒙

山西

Adipokines may act locally (autocrine and paracrine action) or systemically (endocrine action), carrying information about the adequacy of the energy reserves (TAGs) stored in adipose tissue to other tissues and to the brain. Normally, adipokines produce changes in fuel metabolism and feeding behavior that reestablish adequate fuel reserves and maintain body mass. When adipokines are over- or underproduced, the resulting dysregulation may result in life-threatening disease.

Leptin is an adipokine (167 amino acid residues) that, on reaching the brain, acts on receptors in the hypothalamus to curtail appetite. Leptin was first identified as the product of a gene designated OB (obese) in laboratory mice. Mice with two defective copies of this gene ( ob / ob genotype) show the behavior and physiology of animals in a constant state of starvation: their plasma cortisol levels are elevated; they exhibit unrestrained appetite, are unable to stay warm, grow abnormally large, and do not reproduce.

A second mouse gene, designated D B (diabetic), also has a role in appetite regulation. Mice with two defective copies ( db / db ) are obese and diabetic. The D B gene encodes the leptin receptor. When the receptor is defective, the signaling function of leptin is lost. The leptin receptor is expressed primarily in regions of the brain known to regulate feeding behavior—neurons of the arcuate nucleus of the hypothalamus. Leptin carries the message that fat reserves are sufficient, and it promotes reduction of fuel intake and increase in expenditure of energy. Leptin-receptor interaction in the hypothalamus alters the release of neuronal signals to the region of the brain that affects appetite.

Leptin also stimulates the sympathetic nervous system, increasing blood pressure, heart rate, and thermogenesis by uncoupling the mitochondria of brown adipocytes. Recall that the uncoupling protein UCP1 forms a channel in the inner mitochondrial membrane that allows protons to reenter the mitochondrial matrix without passing through the ATP synthase complex. This permits constant oxidation of fuel (fatty acids in a brown or beige adipocyte) without ATP synthesis, dissipating energy as heat and consuming dietary calories or stored fats in potentially very large amounts.