Xiong Y, Tanaka H, Richardson J A, Williams S C, Slaughter C A, Nakamura M, Chen J L, Yanagisawa M
Howard Hughes Medical Institute and Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA.
J Biol Chem. 2001 Jul 27;276(30):28471-7. doi: 10.1074/jbc.M103478200. Epub 2001 May 18.
Leptin is an adipocyte-derived hormone that regulates body fat stores and feeding behavior. In an effort to identify endogenous diffusible modulators of leptin production, we found that endothelin-1 (ET-1) up-regulates leptin expression in adipocytes. ET-1 is as potent and efficacious as insulin in stimulating leptin production in two different adipocyte cell lines. Endothelins stimulate leptin production via the endothelin-A receptor (ET(A)), as judged by a potency rank order of ET-1 ET-3. We detected expression of ET(A) but not ET(B) in both cell lines by Northern blot analysis. In addition, the ET(A)-selective antagonist FR139317 inhibited ET-1-induced leptin expression more potently than did the ET(B)-selective antagonist BQ788. ET-1 and insulin positively interact with each other in increasing leptin production in adipocytes. In primary mouse white fat cells, we detected expression of both ET(A) and ET(B) by Northern blot and in situ hybridization analyses. We conclude that ET-1 stimulates leptin production via the ET(A) receptor in cultured adipocytes.
瘦素是一种由脂肪细胞分泌的激素，可调节体内脂肪储备和进食行为。为了确定瘦素产生的内源性可扩散调节因子，我们发现内皮素-1（ET-1）可上调脂肪细胞中瘦素的表达。在两种不同的脂肪细胞系中，ET-1刺激瘦素产生的效力和效果与胰岛素相当。根据ET-1＞ET-3的效力等级顺序判断，内皮素通过内皮素-A受体（ET(A)）刺激瘦素产生。通过Northern印迹分析，我们在两种细胞系中均检测到ET(A)的表达，但未检测到ET(B)的表达。此外，ET(A)选择性拮抗剂FR139317比ET(B)选择性拮抗剂BQ788更有效地抑制ET-1诱导的瘦素表达。ET-1和胰岛素在增加脂肪细胞中瘦素产生方面存在正性相互作用。在原代小鼠白色脂肪细胞中，通过Northern印迹和原位杂交分析，我们检测到ET(A)和ET(B)的表达。我们得出结论，ET-1通过ET(A)受体刺激培养的脂肪细胞中瘦素的产生。
