Combined leptin actions on adipose tissue and hypothalamus are required to deplete adipocyte fat in lean rats: implications for obesity treatment.
Intense hyperleptinemia completely depletes adipocyte fat of normal rats within 14 days. To determine the mechanism, epididymal fat pads from normal wild-type (+/+) and obese (fa/fa) Zucker Diabetic Fatty (ZDF) donor rats were transplanted into normal +/+ and fa/fa ZDF recipients. Hyperleptinemia induced by adenovirus-leptin administration depleted all fat from native fat pads and from fat transplants from +/+ donors but not from transplants from ZDF(fa/fa) donors with defective leptin receptors. In both native and transplanted +/+ fat pads, large numbers of mitochondria were apparent, and genes involved in fatty acid oxidation were up-regulated. However, +/+ fat pads transplanted into fa/fa recipients did not respond to hyperleptinemia, suggesting lack of an essential leptin-stimulated cohormone(s). In +/+ but not in fa/fa rats, plasma catecholamine levels rose, and both P-STAT3 and P-CREB increased in adipose tissue, suggesting that both direct and indirect (hypothalamic) leptin receptor-mediated actions of hyperleptinemia are involved in depletion of adipocyte fat.
Park
Byung-Hyun
BH
Gifford Laboratories of the Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8854, USA.
Wang
May-Yun
MY
Lee
Young
Y
Yu
Xinxin
X
Ravazzola
Mariella
M
Orci
Lelio
L
Unger
Roger H
RH
D052436:Adipose Tissue, White / Q000378:metabolism* / Q000637:transplantation; D000818:Animals; D002395:Catecholamines / Q000097:blood / Q000502:physiology; D005227:Fatty Acids / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D007031:Hypothalamus / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D020738:Leptin / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D008297:Male; D051379:Mice; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy*; D010084:Oxidation-Reduction; D051381:Rats; D011924:Rats, Zucker; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology; D012995:Solubility; D013851:Thinness / Q000097:blood / Q000235:genetics* / Q000503:physiopathology
D002395:Catecholamines; D005227:Fatty Acids; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C515447:leptin receptor, mouse