Role of leptin in peroxisome proliferator-activated receptor gamma coactivator-1 expression

• Published in: Endocrinology (Philadelphia) Vol. 141; no. 12; pp. 4576 - 4582
• Main Authors: Kakuma, T, Wang, Z W, Pan, W, Unger, R H, Zhou, Y T
• Format: Journal Article
• Language: English
• Published: United States 01-12-2000
• Subjects: Adenoviridae - genetics; Adipocytes - metabolism; Adipose Tissue, Brown - metabolism; Animals; Blotting, Northern; Cells, Cultured; Cloning, Molecular; Cold Temperature; Gene Expression; Gene Transfer, Horizontal; Leptin - deficiency; Leptin - genetics; Leptin - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Obesity - genetics; Obesity - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Rats, Wistar; Rats, Zucker; Recombinant Fusion Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; RNA-Binding Proteins; Transcription Factors - genetics
• ISSN: 0013-7227
• DOI: 10.1210/en.141.12.4576

Peroxisome proliferator-activated receptor-gamma 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 +/+ rats, it rises only 30% in fa/fa rats. Four days after induction of hyperleptinemia (>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 expression in BAT in rodents and that hyperleptinemia rapidly up-regulates its expression, at least in part, by direct action.