Avtor/Urednik		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
Naslov		Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice
Tip		članek
Vir		Cell
Vol. in št.		Letnik 119, št. 1
Leto izdaje		2004
Obseg		str. 121-35
Jezik		eng
Abstrakt		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.
Deskriptorji		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