中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
“健康与疾病的免疫”国际学术研讨会通知      关于有网站冒充本刊网站的声明
《生命科学》 2013, 25(2): 169-175
瘦素信号转导通路在能量代谢平衡中的作用机制
于 月1,尤 佳2,杨 柳1,刘 勇1*
(1 中国科学院上海生命科学研究院营养科学研究所,中国科学院营养与代谢重点实验室,上海 200031;2 乔瑟琳糖尿病中心,波士顿,美国)
摘 要:瘦素(leptin) 是脂肪细胞分泌的细胞因子,通过结合其位于中枢神经系统,特别是下丘脑内特定神经元上的瘦素受体,激活JAK2-STAT3、PI3K 和ERK 等信号转导通路,发挥抑制食欲、促进能量消耗,从而减少脂肪含量的功能,在体重的生理学调节方面具有举足轻重的作用。血液中瘦素的水平与机体的脂肪含量成正比,因而瘦素作为一种“信使”,可以向中枢神经系统反映整个机体能量储存的情况。而在绝大多数肥胖患者的血液中,瘦素的水平虽然很高,但却无法起到抑制食欲和调节能量代谢平衡的作用,呈现出“瘦素抵抗”的病理学状况。由于中枢神经系统是瘦素最主要的直接靶器官,将主要围绕中枢瘦素受体信号转导通路的分子特征和调控功能,简述近年来在机体水平上瘦素与能量平衡研究的最新进展,以期加深对瘦素信号转导机制及其生理学功能的认知,拓展对能量平衡复杂的调控系统的进一步了解,为解析肥胖与代谢疾病发生发展的分子基础提供新的思路。
关键词:瘦素;瘦素受体;瘦素抵抗;能量平衡;肥胖
 
Leptin receptor signaling in energy homeostasis
YU Yue 1, YOU Jia 2, YANG Liu 1, LIU Yong 1*
(1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences; Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; 2 Joslin Diabetes Center, Boston, USA)
Abstract: Leptin, an adipocyte-secreted cytokine, can cross the blood–brain barrier to act through its receptor on many hypothalamic neurons within the central nervous system (CNS), triggering the activation of the JAK/STAT, PI3 kinase, and ERK signaling cascades. Thus, leptin serves to report the body’s nutritional and energy storage states to the brain, and leptin signaling pathways exert critical regulatory effects upon energy balance and body weight control. In most human patients with obesity, circulating leptin levels are chronically elevated. This condition of persistent hyperleptinemia indicates a state of “leptin resistance” that can fuel further body weight gain. Impairment in leptin responsiveness arises from signaling defects through the leptin receptor. Herein, we intend to summarize the recent progresses in the studies for elucidating the signaling mechanisms by which leptin regulates energy homeostasis. A better understanding of the molecular basis of leptin’s physiological actions will provide new insights into the pathogenesis of obesity, and ultimately help to guide our future strategies for the prevention and treatment of chronic metabolic diseases.
Key words: leptin; leptin receptor; leptin resistance; energy balance; obesity
 
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