Havel Peter J
Department of Nutrition, University of California, Davis, Davis, California 95616, USA.
Diabetes. 2004 Feb;53 Suppl 1:S143-51. doi: 10.2337/diabetes.53.2007.s143.
Hormones produced by adipose tissue play a critical role in the regulation of energy intake, energy expenditure, and lipid and carbohydrate metabolism. This review will address the biology, actions, and regulation of three adipocyte hormones-leptin, acylation stimulating protein (ASP), and adiponectin-with an emphasis on the most recent literature. The main biological role of leptin appears to be adaptation to reduced energy availability rather than prevention of obesity. In addition to the well-known consequences of absolute leptin deficiency, subjects with heterozygous leptin gene mutations have low circulating leptin levels and increased body adiposity. Leptin treatment dramatically improves metabolic abnormalities (insulin resistance and hyperlipidemia) in patients with relative leptin deficiency due to lipoatrophy. Leptin production is primarily regulated by insulin-induced changes of adipocyte metabolism. Dietary fat and fructose, which do not increase insulin secretion, lead to reduced leptin production, suggesting a mechanism for high-fat/high-sugar diets to increase energy intake and weight gain. ASP increases the efficiency of triacylglycerol synthesis in adipocytes leading to enhanced postprandial lipid clearance. In mice, ASP deficiency results in reduced body fat, obesity resistance, and improved insulin sensitivity. Adiponectin production is stimulated by thiazolidinedione agonists of peroxisome proliferator-activated receptor-gamma and may contribute to increased insulin sensitivity. Adiponectin and leptin cotreatment normalizes insulin action in lipoatrophic insulin-resistant animals. These effects may be mediated by AMP kinase-induced fat oxidation, leading to reduced intramyocellular and liver triglyceride content. The production of all three hormones is influenced by nutritional status. These hormones, the pathways controlling their production, and their receptors are promising targets for managing obesity, hyperlipidemia, and insulin resistance.
脂肪组织产生的激素在能量摄入、能量消耗以及脂质和碳水化合物代谢的调节中起着关键作用。本综述将探讨三种脂肪细胞激素——瘦素、酰化刺激蛋白（ASP）和脂联素的生物学特性、作用及调节机制，重点关注最新文献。瘦素的主要生物学作用似乎是适应能量供应减少，而非预防肥胖。除了绝对瘦素缺乏的众所周知的后果外，携带杂合瘦素基因突变的受试者循环瘦素水平较低且身体脂肪增加。瘦素治疗可显著改善因脂肪萎缩导致的相对瘦素缺乏患者的代谢异常（胰岛素抵抗和高脂血症）。瘦素的产生主要受胰岛素诱导的脂肪细胞代谢变化调节。不增加胰岛素分泌的膳食脂肪和果糖会导致瘦素产生减少，这提示了高脂/高糖饮食增加能量摄入和体重增加的一种机制。ASP可提高脂肪细胞中三酰甘油合成的效率，从而增强餐后脂质清除。在小鼠中，ASP缺乏会导致体脂减少、抗肥胖和胰岛素敏感性改善。脂联素的产生受过氧化物酶体增殖物激活受体γ的噻唑烷二酮类激动剂刺激，可能有助于提高胰岛素敏感性。脂联素和瘦素联合治疗可使脂肪萎缩性胰岛素抵抗动物的胰岛素作用恢复正常。这些作用可能由AMP激酶诱导的脂肪氧化介导，导致细胞内和肝脏甘油三酯含量降低。所有这三种激素的产生均受营养状况影响。这些激素、控制其产生的途径及其受体是治疗肥胖、高脂血症和胰岛素抵抗的有前景的靶点。
