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

Pharm Res. 2016 Aug;33(8):2033-42. doi: 10.1007/s11095-016-1941-1. Epub 2016 May 9.


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 influence on body composition were analyzed by magnetic residence imaging. Glucose meter and ELISA were used to determine serum glucose and insulin levels, as well as 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.

Keywords: N-acetylcysteine; hepatic steatosis; inflammation; insulin resistance; obesity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use*
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diet, High-Fat / adverse effects*
  • Insulin / blood
  • Male
  • Metabolic Diseases / etiology*
  • Metabolic Diseases / metabolism
  • Metabolic Diseases / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Obesity / drug therapy
  • Obesity / etiology
  • Obesity / metabolism


  • Blood Glucose
  • Insulin
  • Acetylcysteine