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PPARγ coactivator 1β/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity

2003; National Academy of Sciences; Volume: 100; Issue: 21 Linguagem: Inglês

10.1073/pnas.2135217100

1091-6490

Yasutomi Kamei, Hiroshi Ohizumi, Yasushi Fujitani, Tomoyuki Nemoto, Toshiya Tanaka, Nobuyuki Takahashi, Teruo Kawada, Masamitsu Miyoshi, Osamu Ezaki, Akira Kakizuka,

Metabolism, Diabetes, and Cancer

A well balanced body energy budget controlled by limitation of calorie uptake and/or increment of energy expenditure, which is typically achieved by proper physical exercise, is most effective against obesity and diabetes mellitus. Recently, peroxisome proliferator-activated receptor (PPAR) γ, a member of the nuclear receptor, and its cofactors have been shown to be involved in lipid metabolism and in the control of energy expenditure. Here we show that PPARγ coactivator 1 (PGC-1) β functions as ERRL1 (for ERR l igand 1 ), which can bind and activate orphan ERRs (estrogen receptor-related receptors) in vitro . Consistently, PGC-1β/ERRL1 transgenic mice exhibit increased expression of the medium-chain acyl CoA dehydrogenase, a known ERR target and a pivotal enzyme of mitochondrial β-oxidation in skeletal muscle. As a result, the PGC-1β/ERRL1 mice show a state similar to an athlete; namely, the mice are hyperphagic and of elevated energy expenditure and are resistant to obesity induced by a high-fat diet or by a genetic abnormality. These results demonstrate that PGC-1β/ERRL1 can function as a protein ligand of ERR, and that its level contributes to the control of energy balance in vivo , and provide a strategy for developing novel antiobesity drugs.