The purpose of the present study was to examine whether lack of skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) affects the switch in substrate utilization from a fed to fasted state and the fasting-induced pyruvate dehydrogenase (PDH) regulation in skeletal muscle. Skeletal muscle-specific PGC-1α knockout (MKO) mice and floxed littermate controls w...

BACKGROUND Pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF) is an increasingly recognized clinical complication of metabolic syndrome. No adequate animal model of PH-HFpEF is available, and no effective therapies have been identified to date. A recent study suggested that dietary nitrate improves insulin resistance in endothelial nitric oxide synt...

Sirtuin-3 (SIRT3) regulates mitochondrial quality and is involved in the anti-ageing and pro-longevity actions of caloric restriction (CR). Here, we show that CR upregulates the mature form of SIRT3 and mitochondrial intermediate peptidase (MIPEP), a mitochondrial signal peptidase (MtSPase), in white adipose tissue. We also demonstrate that upregulation of mature SIRT3 is dependent on MIPEP in ...

Gut inflammation contributes to the development of gut motility disorders in part by disrupting the function and survival of enteric neurons through mechanisms that involve oxidative stress. How enteric neurons regulate oxidative stress is still poorly understood. Importantly, how neuron autonomous antioxidant mechanisms contribute to the susceptibility of enteric neurons to oxidative stress in...

Sirtuins are emerging as key regulators of many cellular functions including metabolism, cell growth, apoptosis, and genetic control of ageing. In mammals there are seven sirtuin analogues, SIRT1 to SIRT7. Among them SIRT3 is unique because this is the only analogue whose increased expression has been found to be associated with extended lifespan of humans. SIRT3 levels have been shown to be el...

Doxorubicin (Doxo) is a chemotherapeutic drug widely used to treat variety of cancers. One of the most serious side effects of Doxo is its dose-dependent and delayed toxicity to the heart. Doxo is known to induce cardiac mitochondrial damage. Recently, the mitochondrial sirtuin SIRT3 has been shown to protect mitochondria from oxidative stress. Here we show that overexpression of SIRT3 protects...

BACKGROUND Sirtuins (Sirt), a family of nicotinamide adenine nucleotide (NAD) dependent deacetylases, are implicated in energy metabolism and life span. Among the known Sirt isoforms (Sirt1-7), Sirt3 was identified as a stress responsive deacetylase recently shown to play a role in protecting cells under stress conditions. Here, we demonstrated the presence of Sirt3 in neurons, and characterize...

BACKGROUND Emerging evidence indicates that impaired angiogenesis may contribute to hypertension-induced cardiac remodeling. The nicotinamide adenine dinucleotide-dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3-mediated angiogenesis and cardiac remode...

Mitochondria are dynamic organelles whose functions are tightly regulated at multiple levels to maintain proper cellular homeostasis. Mitochondrial Sirtuin 3 (SIRT3), which belongs to an evolutionary conserved family of NAD+-dependent deacetylases, is a key regulator of the mitochondrial respiratory chain, ATP production, and fatty acid β-oxidation, and it exerts an antioxidant activity. Change...