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Resveratrol increases CD68 + Kupffer cells colocalized with adipose differentiation‐related protein and ameliorates high‐fat‐diet‐induced fatty liver in mice
Author(s) -
Nishikawa Kahoko,
Iwaya Keiichi,
Kinoshita Manabu,
Fujiwara Yoko,
Akao Mai,
Sonoda Mariko,
Thiruppathi Suresh,
Suzuki Takayoshi,
Hiroi Sadayuki,
Seki Shuhji,
Sakamoto Toshihisa
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400564
Subject(s) - resveratrol , cd68 , adipose tissue , endocrinology , medicine , kupffer cell , lipid droplet , fatty liver , chemistry , oil red o , hepatic stellate cell , biology , immunohistochemistry , biochemistry , adipogenesis , disease
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.