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Role of Leptin in Peroxisome Proliferator-Activated Receptor Gamma Coactivator1 Expression

Role of Leptin in Peroxisome Proliferator-Activated Receptor Gamma Coactivator1 Expression,TETSUYA KAKUMA,ZHUO-WEI WANG,WENTONG PAN,ROGER H. UNGER,YAN

Role of Leptin in Peroxisome Proliferator-Activated Receptor Gamma Coactivator1 Expression   (Citations: 12)
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Peroxisome proliferator-activated receptor-g coactivator-1 (PGC- 1), a cold-induced protein expressed in brown adipose tissue (BAT), plays a role in adaptive thermogenesis by up-regulating uncoupling proteins (UCP). Here, we explore its relationship to the thermogenic actions of leptin, which also up-regulates UCPs. We find that PGC-1 messenger RNA (mRNA) is markedly reduced in BAT of obese leptin- deficient (ob/ob mice) and leptin-unresponsive (db/db mice and Zucker diabetic fatty fa/fa rats) rodents. Whereas, after cold exposure (6 C for 7 h), PGC-1 mRNA increases 2.6-fold in BAT of lean 1/1 rats, it rises only 30% in fa/fa rats. Four days after induction of hyper- leptinemia (.30 ng/ml) in Wistar rats, by adenovirus gene transfer, PGC-1 mRNA in BAT was 2.3-fold and UCP-1, 4-fold above controls. In isolated white adipocytes, PGC-1 mRNA increased 4.4-fold within 6 h of incubation with 20 ng/ml of leptin. We conclude that leptin action is required for normal basal and cold-stimulated PGC-1 ex- pression in BAT in rodents and that hyperleptinemia rapidly up- regulates its expression, at least in part, by direct action. (Endocri- nology 141: 4576 - 4582, 2000)
Published in 2010.
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