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

Tetsuya Kakuma, Zhuo Wei Wang, P. A N Wentong, Roger H Unger, Yan Ting Zhou

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Peroxisome proliferator-activated receptor-γ 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.

Original languageEnglish (US)
Pages (from-to)4576-4582
Number of pages7
JournalEndocrinology
Volume141
Issue number12
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Endocrinology

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