代谢的整体性(integrationofmetabolism).ppt

Leptin stimulates production of anorexigenic peptide hormones Two types of neurons in the arcuate nucleus control fuel make and metabolism. The orexigenic (appetite-stimulating) neurons stimulate eating by producing and releasing neuropeptide Y (NPY), which causes the next neuron in the circuit to send the signal to the brain, Eat! The blood level of NPY rises during starvation, and is elevated in both ob/ob and db/db mice. Hormones that control eating The JAK-STAT mechanism of leptin signal transduction in the hypothalamus STAT : signal transducers and activators of transcription Adiponectin acts through AMPK Adiponectin is a hormone (224 amino acids) produced almost exclusively in adipose tissue. It circulates in the blood and powerfully affects the metabolism of fatty acids and carbohydrates in liver and muscle. Adiponectin increases the uptake of fatty acids from the blood by myocytes and the rate at which fatty acids undergo b-oxidation in the muscle. It also blocks fatty acid synthesis and gluconeogenesis in hepatocytes, and stimulates glucose uptake and catbolism in muscle and liver. These effects of adiponectin occur indirectly, through activation of the key regulatory enzyme AMPK by increased cytosolic [AMP]. When activated, AMPK phosphorylates a number of target proteins critical to the metabolism of fatty acids and carbohydrates, with profound effects on the metabolism of the whole animal. The role of AMP-activated protein kinase (AMPK) in regulating ATP metabolism Regulation of fatty acid synthesis and b oxidation by AMPK action on acetyl-CoA carboxylase Thiazolidinediones The drug used in treatment of type II diabetes. Increase the expression of adiponectin mRNA in adipose tissue and increase blood adiponectin levels in experimental animals; they are activate AMPK. It appears that adiponectin, acting through AMPK, modulates the sensitivity of cells and tissues to insulin. The factors improve the health of individuals with type II diabetes Regular exer