This framework may help identify novel approaches for promoting chondrocyte homeostasis during aging and obesity.<b>Materials and Methods</b>: Changes in glutathione content and redox ratio were evaluated in three models of chondrocyte stress: (1) age- and tissue-specific changes in joint tissues of 10 and 30-month old F344BN rats, including <i>ex vivo</i> patella culture experiments to evaluate N-acetylcysteine dependent resistance to interleukin-1beta; (2) effect of different durations and patterns of cyclic compressive loading in bovine cartilage on glutathione stress resistance and resilience pathways; (3) time-dependent changes in GSH:GSSG in primary chondrocytes from wild-type and Sirt3 deficient mice challenged with the pro-oxidant menadione.<b>Results</b>: Glutathione was more abundant in cartilage than meniscus or infrapatellar fat pad, although cartilage was also more susceptible to age-related glutathione oxidation.
The studies on mice show that Sirt3 SUMOylation mutation reduces fat mass and antagonizes high-fat diet (HFD)-induced obesity via increasing oxidative phosphorylation and energy expenditure.
Myocardial tissue samples from patients with left ventricular heart failure, with either obesity or normal weight, were processed for the expression of SIRT3 and acetylation profile by Western Blot (WB).
We found that expression of both Sirt6 and Sirt3 was reduced in cardiomyocytes treated with palmitate and in hearts of mice fed with a high-fat, high-sucrose (HF-HS) diet to develop obesity and diabetes.
The aim of present study was to test the hypothesis that nicotinamide adenine dinucleotide (NAD<sup>+</sup>)-dependent deacetylase sirtuin-3 (SIRT3) in adipocytes plays a critical role in adipose tissue mitochondrial biology and obesity.
Improving mitochondrial SIRT3 functions by inhibiting SIRT3 acetylation may offer a new therapeutic approach for obesity- and aging-related diseases associated with mitochondrial dysfunction.
Taken together, our findings suggest that SIRT3 positively regulates endothelial insulin sensitivity and show that SIRT3 deficiency and resultant increased mtROS contribute to vascular dysfunction in obesity.
Mice lacking SIRT3 (SIRT3KO) placed on a HFD show accelerated obesity, insulin resistance, hyperlipidemia, and steatohepatitis compared to wild-type (WT) mice.