Endothelin-1 stimulates leptin production in adipocytes.
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.
Xiong
Y
Y
Howard Hughes Medical Institute and Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA.
Tanaka
H
H
Richardson
J A
JA
Williams
S C
SC
Slaughter
C A
CA
Nakamura
M
M
Chen
J L
JL
Yanagisawa
M
M
D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism*; D016232:Endothelins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D020738:Leptin / Q000096:biosynthesis*; D008024:Ligands; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism; D054411:Receptors, Leptin; D015854:Up-Regulation
D019332:Endothelin-1; D016232:Endothelins; D007328:Insulin; D020738:Leptin; D008024:Ligands; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D054411:Receptors, Leptin; C515447:leptin receptor, mouse