Abstract
Sirt6 is a member of the sirtuin family involved in physiological and pathological processes including aging, cancer, obesity, diabetes, and energy metabolism. This study is aimed at evaluating the relationship between liver SIRT6 gene expression and the oxidative stress network depending on adiposity levels in Zucker rats, an animal model of metabolic syndrome. We observed that liver-specific SIRT6 expression is reduced in an in vivo model of spontaneous obesity and metabolic syndrome. We also observed that SIRT6 expression in the liver is positively associated with SIRT1 and GST-M2 expressions, two proteins involved in antioxidant protection pathways and inversely related to body weight and plasmatic oxidative status. Interestingly, the SIRT6 expression is upregulated after energy restriction-induced weight loss concomitantly with an improvement in oxidative stress markers. These results suggest that SIRT6 may be a potential therapeutic target for the treatment of obesity and associated metabolic disorders, such as liver disease.
Highlights
During the last years, numerous evidences suggested the oxidative stress as a key factor involved in the development of obesity and its comorbidities [1]
The oxidative stress in obesity is induced by an excessive generation and accumulation of reactive oxygen species (ROS) in different cellular structures due to the expansion of the adipose tissue and inefficiency in the energy metabolism leading to cellular damage [2, 3]
This work shows that the oxidative stress induced by excess of adiposity is related to a downregulation of hepatic SIRT6 expression in obese individuals
Summary
Numerous evidences suggested the oxidative stress as a key factor involved in the development of obesity and its comorbidities [1]. The metabolic syndrome associated with obesity identifies subjects who have an increase in morbidity and mortality and is correlated with the development of several pathologies that affect different organs such as the liver and the progression from steatosis to nonalcoholic steatohepatitis and hepatocarcinogenesis in which oxidative stress appears to be involved [4]. Sirtuins are a family of NAD+-dependent protein deacetylases and ADP-ribosyltransferases with an important role in regulating the life span, aging, and cancer as well as energy metabolism and obesity and its metabolic associated disorders [5] and have been proposed as a possible target for future therapies against these diseases. A number of studies revealed that Sirt has several beneficial effects on metabolic cell control and enhances the ability of cells to cope
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