Resveratrol increases CD68⁺ Kupffer cells colocalized with adipose differentiation-related protein and ameliorates high-fat-diet-induced fatty liver in mice

Mol Nutr Food Res. 2015 Jun;59(6):1155-70. doi: 10.1002/mnfr.201400564. Epub 2015 May 18.

Abstract

Scope: Resveratrol reportedly improves fatty liver. This study purposed to elucidate the effect of resveratrol on fatty liver in mice fed a high-fat (HF) diet, and to investigate the role of liver macrophages (Kupffer cells).

Methods and results: C57BL/6 mice were divided into three groups, receiving either a control diet, HF diet (50% fat), or HF supplemented with 0.2% resveratrol (HF + res) diet, for 8 weeks. Compared with the HF group, the HF + res group exhibited markedly attenuated fatty liver, and reduced lipid droplets (LDs) in hepatocytes. Proteomic analysis demonstrated that the most downregulated protein in the livers of the HF + res group was adipose differentiation-related protein (ADFP), which is a major constituent of LDs and reflects lipid accumulation in cells. The HF + res group exhibited greatly increased numbers of CD68(+) Kupffer cells with phagocytic activity. Immunohistochemistry showed that several CD68(+) Kupffer cells were colocalized with ADFP immunoreaction in the HF + res group. Additionally, the HF + res group demonstrated markedly decreased TNF-alpha production, which confirmed by both liver mononuclear cells stimulated by LPS in vitro and in situ hybridization analysis, compared with the HF group.

Conclusion: Resveratrol ameliorated fatty liver and increased CD68-positive Kupffer cells with downregulating ADFP expression.

Keywords: Fatty liver; Kupffer cells; Lipid droplets; Lipid metabolism; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Diet, High-Fat / adverse effects
  • Down-Regulation
  • Fatty Liver / drug therapy*
  • Kupffer Cells / drug effects*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Organ Size / drug effects
  • Perilipin-2
  • Proteomics
  • Resveratrol
  • Stilbenes / pharmacology*
  • Triglycerides / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 protein, mouse
  • Membrane Proteins
  • Perilipin-2
  • Plin2 protein, mouse
  • Stilbenes
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Resveratrol