Endurance exercise stimulates peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) expression in skeletal muscle, and forced expression of PGC-1alpha changes muscle metabolism and exercise capacity in mice. However, it is unclear if PGC-1alpha is indispensible for endurance exercise-induced metabolic and contractile adaptations in skeletal muscle. In this study, we s...

Neurons rely heavily on mitochondria for their function and survival. Mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases such as Parkinson's disease. PGC-1α is a master regulator of mitochondrial biogenesis and function. Here we identify necdin as a potent PGC-1α stabilizer that promotes mitochondrial biogenesis via PGC-1α in mammalian neurons. Expression of...

Huntington's disease (HD) is a fatal, dominantly inherited disorder caused by polyglutamine repeat expansion in the huntingtin (htt) gene. Here, we observe that HD mice develop hypothermia associated with impaired activation of brown adipose tissue (BAT). Although sympathetic stimulation of PPARgamma coactivator 1alpha (PGC-1alpha) was intact in BAT of HD mice, uncoupling protein 1 (UCP-1) indu...

OBJECTIVE We examined whether skeletal muscle overexpression of PGC-1α1 or PGC-1α4 affected myokine secretion and neuromuscular junction (NMJ) formation. METHODS A microfluidic device was used to model endocrine signaling and NMJ formation between primary mouse myoblast-derived myotubes and embryonic stem cell-derived motor neurons. Differences in hydrostatic pressure allowed for fluidic isol...

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has been shown to influence energy metabolism. Hence, we explored a strategy to target PGC-1α expression to treat metabolic syndromes. We developed a high-throughput screening assay that uses the human PGC-1α promoter to drive expression of luciferase. The effects of lead compound stimulation on PGC-1α expression in muscle cel...

Increasing evidences have accumulated that endothelial dysfunction is involved in the pathogenesis of hypertension. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) has been identified as an essential factor that protects against endothelial dysfunction in vascular pathologies. However, the functional role of PGC-1α in hypertension is not well understood. Using an ad...

AngII (angiotensin II)-induced excessive ROS (reactive oxygen species) generation and proliferation of VSMCs (vascular smooth muscle cells) is a critical contributor to the pathogenesis of atherosclerosis. PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator-1α] is involved in the regulation of ROS generation, VSMC proliferation and energy metabolism. The aim of the present...

The relationship between systemic blood pressure and glomerular capillary pressure (Pgc) in spontaneously hypertensive rats (SHR) during treatment with antihypertensive drugs is still unclear. The effects of an angiotensin-converting enzyme inhibitor (enalapril), two calcium channel antagonists (nifedipine and verapamil), and an α1-receptor blocker (doxazosin) on renal blood flow (RBF) autoregu...

PGC-1β plays pleiotropic roles in regulating intermediary metabolism and has been shown to regulate both catabolic and anabolic processes in liver. We sought to evaluate the effects of PGC-1β on liver energy metabolism by generating mice with postnatal, liver-specific deletion of PGC-1β (LS-PGC-1β(-/-) mice). LS-PGC-1β(-/-) mice were outwardly normal, but exhibited a significant increase in hep...

PPARdelta (peroxisome proliferator-activated receptor delta) is a regulator of lipid metabolism and has been shown to induce fatty acid oxidation (FAO). PPARdelta transgenic and knock-out mice indicate an involvement of PPARdelta in regulating mitochondrial biogenesis and oxidative capacity; however, the precise mechanisms by which PPARdelta regulates these pathways in skeletal muscle remain un...