N-acetylcysteine Protects Mice from High Fat Diet-induced Metabolic Disorders

Abstract

Purpose To study the effects of N-acetylcysteine (NAC, C5H9NO3S) on diet-induced obesity and obesity-related metabolic disorders. Methods Six-week-old male C57BL/6 mice fed a chow or high-fat diet (HFD) were treated with NAC (2 g/L) in drinking water for 11 weeks. Its influences on body weight, and food intake were manually measured and on body composition were analyzed by magnetic residence imaging. Glucose meter and ELISA were used to determine serum glucose and insulin levels, and lipid content in the liver. The effects of NAC treatment on mRNA levels of genes involved in inflammation, thermogenesis, and lipid metabolism in various tissues were determined by real time PCR. Results NAC supplementation inhibited the increase of fat mass and the development of obesity when mice were fed an HFD. NAC treatment significantly lowered HFD-induced macrophage infiltration, and enhanced adiponectin gene expression, resulting in reduced hyperglycemia and hyperinsulinemia, and improvement of insulin resistance. NAC oral administration suppressed hepatic lipid accumulation as evidenced by lower levels of triglyceride and cholesterol in the liver. The beneficial effects are associated with a decrease of hepatic Pparγ and its target gene expression, and an increase in the expression of genes responsible for lipid oxidation and activation of farnesoid X receptor. Furthermore, NAC treatment also stimulates expression of thermogenic genes. Conclusion These results provide direct proof of the protective potential of NAC against HFD-induced obesity and obesity-associated metabolic disorders.

Reduction of oxidative stress improves insulin signaling in cardiac tissue of obese mice

“…The administration of the antioxidant NAC did not significantly alter the body weight of these animals. On the other hand, when NAC was administered concomitantly to the high fat diet, Ma et al, (22) observed a reduction in body weight of the Group Treated with NAC, as compared to the non-treated obese group.…”

Antioxidant therapy for muscular dystrophy: caveat lector!

“…Ma et al . () reported decreases in epididymal and subcutaneous white adipose tissue, as well as decreased adipocyte expansion in brown adipose tissue and evidence of altered thermogenic gene expression suggesting increased energy expenditure following chronic NAC supplementation. Interestingly, however, notwithstanding changes culminating in altered body composition, Ma et al .…”

“…Interestingly, however, notwithstanding changes culminating in altered body composition, Ma et al . () reported that NAC supplementation at 2% in the drinking water for 11 weeks beginning at 6 weeks of age did not affect body mass at any time point, whereas Cao & Picklo () observed that 1 g kg −1 NAC in the diet decreased body mass after 5 weeks of supplementation, although the effects were modest after 17 weeks of supplementation. It was also previously reported that NAC supplementation decreased body mass in a dose‐dependent manner (Kim et al .…”

N-acetyl Cysteine Can Blunt Metabolic and Cardiovascular Effects via Down-regulation of Cardiotrophin-1 in Rat Model of Fructose-induced Metabolic Syndrome

“…Accumulating experimental evidence indicated that NAC promoted adiponectin gene expression, resulting in reduced hyperglycemia and hyperinsulinemia, and amelioration of IR [21,26]. The principal mechanisms by which adiponectin improve insulin sensitivity seems to be through augmented fatty acid oxidation and suppression of hepatic glucose production [24].…”