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

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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 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.

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Abbreviations

ANOVA:

Analysis of variance

BAT:

Brown adipose tissue

CD68:

Cluster of differentiation 68

Cox2:

Cyclooxygenase 2

Cpt1:

Carnitine palmitoyltransferase 1

Cyp7a1:

Cholesterol 7 alpha-hydroxylase

Dio2:

Type II iodothyronine deiodinase

FXR:

Farnesoid X receptor

Gapdh:

Glyceraldehyde-3-Phosphate Dehydrogenase

GTT:

Glucose tolerance test

H&E:

Haematoxylin and eosin stain

HDL:

High-density lipoprotein

HFD:

High fat diet

Inos:

Inducible nitric oxide synthase

ITT:

Insulin tolerance test

LDL:

Low-density lipoprotein

LPS:

Lipopolysaccharide

Mcp1:

Monocyte chemotactic protein 1

Mgat1:

Monoacylglycerol O-acyltransferase 1

NADPH:

Nicotinamide adenine dinucleotide phosphate

Pgc1α:

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

Ppar:

Peroxisome proliferator-activated receptor

RT-PCR:

Real time PCR

SD:

Standard deviation

Shp:

Small heterodimer partner

Tnfα:

Tumor necrosis factor alpha

Ucp:

Uncoupling Protein

WAT:

White adipose tissue

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Acknowledgments and Disclosures

We thank Mrs. Francisca Burnley for proofreading and English editing. This work was supported in part by the National Institute of Health [RO1 HL098295].

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Authors and Affiliations

  1. Department of Pharmaceutical and Biomedical Sciences, University of Georgia College of Pharmacy, Athens, Georgia, USA

    Yongjie Ma, Mingming Gao & Dexi Liu

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  1. Yongjie Ma
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  3. Dexi Liu
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Corresponding author

Correspondence to Dexi Liu.

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Fig. S1

NAC treatment represses LPS-induced expression of inflammation response genes in macrophages. RAW264.7 cells were treated with LPS (100 ng/ml) in the presence of various doses of NAC for 24 h. Cells were harvested and total RNA was extracted for RT-PCR analysis. Relative mRNA levels of (a) Inos; (b) Cox2; (c) Mcp1; and (d) Tnfα. **P < 0.01 compared to LPS treatment without NAC (n = 3). (GIF 50 kb)

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Ma, Y., Gao, M. & Liu, D. N-acetylcysteine Protects Mice from High Fat Diet-induced Metabolic Disorders. Pharm Res 33, 2033–2042 (2016). https://doi.org/10.1007/s11095-016-1941-1

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  • DOI: https://doi.org/10.1007/s11095-016-1941-1

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