Ex vivo Anti-Senescence Activity of N-Acetylcysteine in Visceral Adipose Tissue of Obese Volunteers.

INTRODUCTION: Excessive visceral adiposity is known to drive the onset of metabolic derangements, mostly involving oxidative stress, prolonged inflammation, and cellular senescence. N-acetylcysteine (NAC) is a synthetic form of l-cysteine with potential antioxidant, anti-inflammatory, and anti-senescence properties. This ex-vivo study aimed to determine the effect of NAC on some markers of senescence including ß-galactosidase activity and p16, p53, p21, IL-6, and TNF-α gene expressions in visceral adipose tissue in obese adults. METHODS: This ex-vivo experimental study involved 10 obese participants who were candidates for bariatric surgery. Duplicate biopsies from the abdominal visceral adipose tissue were obtained from the omentum. The biopsies were treated with or without NAC (5 and 10 mm). To evaluate adipose tissue senescence, beta-galactosidase (ß-gal) activity and the expression of P16, P21, P53, IL-6, and TNF-α were determined. ANOVA test was employed to analyze the varying markers of cellular senescence and inflammation between treatment groups. RESULTS: The NAC at concentrations of 5 mm and 10 mm resulted in a noteworthy reduction ß-gal activity compared to the control group (p < 0.001). Additionally, the expression of P16, P21, and IL-6 was significantly reduced following treatment with NAC (5 mm) and NAC (10 mm) compared to the control group (All p < 0.001). DISCUSSION/CONCLUSION: Taken together, these data suggest the senotherapeutic effect of NAC, as it effectively reduces the activity of SA-ß-gal and the expression of IL-6, P16, and P21 genes in the visceral adipose tissue of obese individuals.

Effects of N-acetylcysteine on aging cell and obesity complications in obese adults: a randomized, double-blind clinical trial.

Background: We decided to conduct this study with the aim of investigating the effects of N-Acetylcysteine (NAC) on obesity complications and senescence of visceral adipose tissue in obese adults. Methods and analysis: The present study was conducted as a randomized clinical trial (RCT) (Clinical trial registry number: IRCT20220727055563N1) on 40 obese adults candidates for bariatric surgery, who were randomly assigned to receive 600 mg of NAC (n = 20) or placebo as a control (n = 20) for 4 weeks. During bariatric surgery, visceral adipose tissue was used to examine gene expression and senescence cells using SA-ß-gal. Results: Our findings showed that intervention with NAC significantly reduces SA-ß-gal activity (as a marker of senescence) and expression of p16 and interleukin 6 (IL-6) genes in the visceral adipose tissue compared to placebo in obese adults for 4 weeks. In addition, our findings showed the potential and beneficial effect of NAC administration on reducing the levels of inflammatory factors including IL-6 and high-sensitivity C-reactive protein (hs-CRP), as well as the level of fasting blood sugar (FBS), homeostatic model assessment of insulin resistance (HOMA-IR), and insulin compared to placebo after adjusting for confounders. No significant effect was indicated on anthropometric factors and lipid profile. Conclusion: Findings showed that NAC, in addition to having a potential beneficial effect on reducing some of the complications caused by obesity, seems to have synolytic/senomorphic potential as well. Clinical trial registration: [https://clinicaltrials.gov/], identifier [IRCT20220727055563N1].