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

• Published in: Molecular nutrition & food research 2015-06, Vol.59 (6), p.1155-1170
• Main Authors: Nishikawa, Kahoko, Iwaya, Keiichi, Kinoshita, Manabu, Fujiwara, Yoko, Akao, Mai, Sonoda, Mariko, Thiruppathi, Suresh, Suzuki, Takayoshi, Hiroi, Sadayuki, Seki, Shuhji, Sakamoto, Toshihisa
• Format: Article
• Language: English
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201400564

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 super(+) Kupffer cells with phagocytic activity. Immunohistochemistry showed that several CD68 super(+) 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.