Resistance to high-fat diet-induced obesity in male heterozygous Pprc1 knockout mice.

Peroxisome proliferator-activated receptor gamma, co-activator-related 1 (Pprc1) is the third member of the Pgc1 family. Other than the well-characterized Pgc1a and Pgc1b that act as regulators of mitochondrial biogenesis and oxidative metabolism, the function of Pprc1 in vivo is rarely reported, due to embryonic lethality of whole-body Pprc1 knockout mice. To investigate the biological and physiological function of Pprc1 in metabolic processes, male Pprc1(+/-) mice fed with a high fat diet (HFD) showed resistance to diet-induced obesity with a decrease of adipose tissue in Pprc1(+/-) mice, which was a result of elevated energy expenditure. In skeletal muscle of Pprc1(+/-) mice, Pprc1 level showed haplo-insufficiency with down-regulation of Pgc1b and Pgc1a, whereas in adipose tissue, Pprc1 expression remained normal, with significant compensatory increase of other Pgc1 family members to induce an up-regulation of respiratory chain genes. Taken together, as the first report on the metabolic roles of Pprc1 in vivo, these results indicated an elevated basal metabolic rate and lipid metabolic alteration of male Pprc1(+/-) mice on HFD, suggesting the significant role of Pprc1 in controlling mitochondrial gene expression and energy metabolic processes, synergistically with Pgc1a and Pgc1b.

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