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

被引:61
作者
Kakuma, T
Wang, ZW
Pan, WT
Unger, RH
Zhou, YT
机构
[1] Univ Texas, SW Med Ctr, Dept Internal Med, Touchstone Ctr Diabet Res,Gifford Labs, Dallas, TX 75235 USA
[2] Vet Affairs N Texas Healthcare Syst, Dallas, TX 75216 USA
关键词
D O I
10.1210/en.141.12.4576
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 BET of obese leptin-deficient (ob/ob mice) and leptin-unresponsive (db/db mice and Zucker diabetic fatty fa/fa rats) rodents. Whereas, after cord 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 alter 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 upregulates its expression, at least in part, by direct action.
引用
收藏
页码:4576 / 4582
页数:7
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