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

Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1), a c old-induced protein expressed in brown adipose tissue (BAT), plays a role i n adaptive thermogenesis by up-regulating uncoupling proteins (UCP). Here, we explore its relationship to the thermogenic actions of leptin, which als o up-regulates UCPs. We find that PGC-1 messenger RNA (mRNA) is markedly re duced 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 hype rleptinemia (>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 whit e adipocytes, PGC-1 mRNA increased 4.4-fold within 6 h of incubation with 2 0 ng/ml of leptin. We conclude that leptin action is required for normal ba sal and cold-stimulated PGC-1 expression in BAT in rodents and that hyperle ptinemia rapidly upregulates its expression, at least in part, by direct ac tion.