PGC-1beta controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis.
The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1beta (PGC-1beta) 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-1beta protein [PGC-1beta knockout (KO) mice]. PGC-1beta 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-1alpha KO mice that are reportedly hyperactive, PGC-1beta 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-1beta in mouse plays a nonredundant role in controlling mitochondrial oxidative energy metabolism.
Sonoda
Junichiro
J
Howard Hughes Medical Institute and Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Mehl
Isaac R
IR
Chong
Ling-Wa
LW
Nofsinger
Russell R
RR
Evans
Ronald M
RM
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001481:Basal Metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D003080:Cold Temperature; D004032:Diet; D015536:Down-Regulation / Q000235:genetics; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism*; D020869:Gene Expression Profiling; D018390:Gene Targeting; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000502:physiology*; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors