Houseknecht K L, Baile C A, Matteri R L, Spurlock M E
Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
J Anim Sci. 1998 May;76(5):1405-20. doi: 10.2527/1998.7651405x.
Leptin, a 16-kDa protein secreted from white adipocytes, has been implicated in the regulation of food intake, energy expenditure, and whole-body energy balance in rodents and humans. The gene encoding leptin was identified by positional cloning and is the mutation leading to the profound obese phenotype of the ob/ob mouse. Exogenous administration of leptin to ob/ob mice leads to a significant improvement in reproductive and endocrine status as well as reduced food intake and weight loss. The expression and secretion of leptin is highly correlated with body fat mass and adipocyte size. Cortisol and insulin are potent stimulators of leptin expression, and expression is attenuated by beta-adrenergic agonists, cAMP, and thiazolidinediones. The role of other hormones and growth factors in the regulation of leptin expression and secretion is emerging. Leptin circulates specifically bound to proteins in serum, which may regulate its half-life and biological activity. Isoforms of the leptin receptor, members of the interleukin-6 cytokine family of receptors, are found in multiple tissues, including the brain. Many of leptin's effects on food intake and energy expenditure are thought to be mediated centrally via neurotransmitters such as neuropeptide Y. Multiple peripheral effects of leptin have also been recently described, including the regulation of insulin secretion by pancreatic beta cells and regulation of insulin action and energy metabolism in adipocytes and skeletal muscle. Leptin is thought to be a metabolic signal that regulates nutritional status effects on reproductive function. Leptin also plays a major role in hematopoeisis and in the anorexia accompanying an acute cytokine challenge. The profound effects of leptin on regulating body energy balance make it a prime candidate for drug therapies for humans and animals.
瘦素是一种由白色脂肪细胞分泌的16千道尔顿蛋白质，在调节啮齿动物和人类的食物摄入、能量消耗及全身能量平衡方面发挥作用。编码瘦素的基因通过定位克隆得以确定，该基因突变会导致ob/ob小鼠出现严重肥胖表型。给ob/ob小鼠外源性注射瘦素可显著改善其生殖和内分泌状态，同时减少食物摄入并减轻体重。瘦素的表达和分泌与体脂量及脂肪细胞大小高度相关。皮质醇和胰岛素是瘦素表达的有效刺激因子，而β-肾上腺素能激动剂、环磷酸腺苷（cAMP）和噻唑烷二酮类药物会使其表达减弱。其他激素和生长因子在调节瘦素表达和分泌方面的作用也逐渐显现。瘦素在血清中与蛋白质特异性结合进行循环，这可能会调节其半衰期和生物活性。瘦素受体的亚型属于白细胞介素-6细胞因子受体家族，在包括大脑在内的多个组织中都有发现。瘦素对食物摄入和能量消耗的许多影响被认为是通过神经递质如神经肽Y在中枢介导的。最近还描述了瘦素的多种外周作用，包括胰腺β细胞对胰岛素分泌的调节以及脂肪细胞和骨骼肌中胰岛素作用和能量代谢的调节。瘦素被认为是一种代谢信号，可调节营养状况对生殖功能的影响。瘦素在造血过程以及急性细胞因子刺激引发的厌食症中也起主要作用。瘦素对调节身体能量平衡的深远影响使其成为人类和动物药物治疗的主要候选对象。
