PGC-1[beta] controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis

The transcriptional coactivator peroxisome proliferator-activated receptor-... coactivator 1β (PGC-1β) is believed to control mitochondrial oxidative energy metabolism by activating specific target transcription factors including estrogen-related receptors and nuclear respiratory factor 1, yet its physiological role is not yet clearly understood. To define its function in vivo, we generated and characterized mice lacking the functional PGC-1β protein [PGC-1β knockout (KO) mice]. PGC-1β KO mice are viable and fertile and show no overt phenotype under normal laboratory conditions. However, the KO mice displayed an altered expression in a large number of nuclear-encoded genes governing mitochondrial and metabolic functions in multiple tissues including heart, skeletal muscle, brain, brown adipose tissue, and liver. In contrast to PGC-1α KO mice that are reportedly hyperactive, PGC-1β KO mice show greatly decreased activity during the dark cycle. When acutely exposed to cold, the KO mice developed abnormal hypothermia and morbidity. Furthermore, high-fat feeding induced hepatic steatosis and increased serum triglyceride and cholesterol levels in the KO mice. These results suggest that PGC-1β in mouse plays a nonredundant role in controlling mitochondrial oxidative energy metabolism. (ProQuest-CSA LLC: ... denotes formulae/symbols omitted.)