Author/Editor		Lin, Jiandie; Wu, Pei-Hsuan; Tarr, Paul T; Lindenberg, Katrin S; St-Pierre, Julie; Zhang, Chen-Yu; Mootha, Vamsi K; Jager, Sibylle; Vianna, Claudia R; Krainc, Dimitri
Title		Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
Type		članek
Source		Cell
Vol. and No.		Letnik 119, št. 1
Publication year		2004
Volume		str. 121-35
Language		eng
Abstract		PGC-1alpha is a coactivator of nuclear receptors and other transcription factors that regulates several metabolic processes, including mitochondrial biogenesis and respiration, hepatic gluconeogenesis, and muscle fiber-type switching. We show here that, while hepatocytes lacking PGC-1alpha are defective in the program of hormone-stimulated gluconeogenesis, the mice have constitutively activated gluconeogenic gene expression that is completely insensitive to normal feeding controls. C/EBPbeta is elevated in the livers of these mice and activates the gluconeogenic genes in a PGC-1alpha-independent manner. Despite having reduced mitochondrial function, PGC-1alpha null mice are paradoxically lean and resistant to diet-induced obesity. This is largely due to a profound hyperactivity displayed by the null animals and is associated with lesions in the striatal region of the brain that controls movement. These data illustrate a central role for PGC-1alpha in the control of energy metabolism but also reveal novel systemic compensatory mechanisms and pathogenic effects of impaired energy homeostasis.
Descriptors		ADAPTATION, PHYSIOLOGICAL ANIMALS APPETITE REGULATION BASAL GANGLIA DISEASES BRAIN CORPUS STRIATUM ENERGY METABOLISM GENE EXPRESSION REGULATION GLUCONEOGENESIS GLUCOSE HOMEOSTASIS HYPERKINESIS LIVER MICE MICE, KNOCKOUT MITOCHONDRIA NEURONS OBESITY TRANS-ACTIVATORS