Havel Peter J
Department of Nutrition, University of California, Davis, California 95616, USA.
Curr Opin Lipidol. 2002 Feb;13(1):51-9. doi: 10.1097/00041433-200202000-00008.
Adipose tissue performs complex metabolic and endocrine functions. This review will focus on the recent literature on the biology and actions of three adipocyte hormones involved in the control of energy homeostasis and insulin action, leptin, acylation-stimulating protein, and adiponectin, and mechanisms regulating their production. Results from studies of individuals with absolute leptin deficiency (or receptor defects), and more recently partial leptin deficiency, reveal leptin's critical role in the normal regulation of appetite and body adiposity in humans. The primary biological role of leptin appears to be adaptation to low energy intake rather than a brake on overconsumption and obesity. Leptin production is mainly regulated by insulin-induced changes of adipocyte metabolism. Consumption of fat and fructose, which do not initiate insulin secretion, results in lower circulating leptin levels, a consequence which may lead to overeating and weight gain in individuals or populations consuming diets high in energy derived from these macronutrients. Acylation-stimulating protein acts as a paracrine signal to increase the efficiency of triacylglycerol synthesis in adipocytes, an action that results in more rapid postprandial lipid clearance. Genetic knockout of acylation-stimulating protein leads to reduced body fat, obesity resistance and improved insulin sensitivity in mice. The primary regulator of acylation-stimulating protein production appears to be circulating dietary lipid packaged as chylomicrons. Adiponectin increases insulin sensitivity, perhaps by increasing tissue fat oxidation resulting in reduced circulating fatty acid levels and reduced intramyocellular or liver triglyceride content. Adiponectin and leptin together normalize insulin action in severely insulin-resistant animals that have very low levels of adiponectin and leptin due to lipoatrophy. Leptin also improves insulin resistance and reduces hyperlipidemia in lipoatrophic humans. Adiponectin production is stimulated by agonists of peroxisome proliferator-activated receptor-gamma; an action may contribute to the insulin-sensitizing effects of this class of compounds. The production of all three hormones is influenced by nutritional status. These adipocyte hormones, the pathways controlling their production, and their receptors represent promising targets for managing obesity, hyperlipidemia, and insulin resistance.
脂肪组织具有复杂的代谢和内分泌功能。本综述将聚焦于近期有关三种参与能量稳态调控及胰岛素作用的脂肪细胞激素（瘦素、酰化刺激蛋白和脂联素）的生物学特性与作用，以及调节它们产生的机制的文献。对绝对瘦素缺乏（或受体缺陷）个体以及近期部分瘦素缺乏个体的研究结果显示，瘦素在人体食欲和体脂的正常调节中起关键作用。瘦素的主要生物学作用似乎是适应低能量摄入，而非抑制过度进食和肥胖。瘦素的产生主要受胰岛素诱导的脂肪细胞代谢变化调节。摄入脂肪和果糖不会引发胰岛素分泌，会导致循环瘦素水平降低，这一结果可能致使食用富含这些宏量营养素所提供能量的饮食的个体或人群出现暴饮暴食和体重增加。酰化刺激蛋白作为旁分泌信号，可提高脂肪细胞中三酰甘油合成的效率，此作用会使餐后脂质清除更快。酰化刺激蛋白基因敲除会导致小鼠体脂减少、抗肥胖且胰岛素敏感性提高。酰化刺激蛋白产生的主要调节因子似乎是作为乳糜微粒包装的循环膳食脂质。脂联素可提高胰岛素敏感性，可能是通过增加组织脂肪氧化，从而降低循环脂肪酸水平以及减少肌细胞内或肝脏甘油三酯含量。脂联素和瘦素共同作用可使因脂肪萎缩而脂联素和瘦素水平极低的严重胰岛素抵抗动物的胰岛素作用恢复正常。瘦素还可改善脂肪萎缩患者的胰岛素抵抗并降低高脂血症。过氧化物酶体增殖物激活受体γ的激动剂可刺激脂联素的产生；这一作用可能有助于这类化合物的胰岛素增敏效应。所有这三种激素的产生均受营养状况影响。这些脂肪细胞激素、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。
