title: Resveratrol increases CD68⁺ Kupffer cells colocalized with adipose differentiation-related protein and ameliorates high-fat-diet-induced fatty liver in mice.
abstract: METHODS
  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).
  
  
  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.
  
  
  CONCLUSIONS
  Resveratrol ameliorated fatty liver and increased CD68-positive Kupffer cells with downregulating ADFP expression.
authors: Faculty of Commerce, Chuo University, Tokyo, Japan.
authors: Kahoko
authors: K
authors: Nishikawa
authors: Department of Basic Pathology, National Defense Medical College, Saitama, Japan.
authors: Keiichi
authors: K
authors: Iwaya
authors: Department of Immunology and Microbiology, National Defense Medical College, Saitama, Japan.
authors: Manabu
authors: M
authors: Kinoshita
authors: Department of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors: Yoko
authors: Y
authors: Fujiwara
authors: Department of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors: Mai
authors: M
authors: Akao
authors: Department of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors: Mariko
authors: M
authors: Sonoda
authors: Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Japan.
authors: Suresh
authors: S
authors: Thiruppathi
authors: Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Japan.
authors: Takayoshi
authors: T
authors: Suzuki
authors: Department of Laboratory Medicine, National Defense Medical College, Saitama, Japan.
authors: Sadayuki
authors: S
authors: Hiroi
authors: Department of Immunology and Microbiology, National Defense Medical College, Saitama, Japan.
authors: Shuhji
authors: S
authors: Seki
authors: Department of Traumatology and Critical Care Medicine, National Defense Medical College, Saitama, Japan.
authors: Toshihisa
authors: T
authors: Sakamoto
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D015536:Down-Regulation; D005234:Fatty Liver / Q000188:drug therapy*; D007728:Kupffer Cells / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D000070780:Perilipin-2; D040901:Proteomics; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D008565:Membrane Proteins; D000070780:Perilipin-2; D000077185:Resveratrol; D013267:Stilbenes; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C000602983:Plin2 protein, mouse
keywords: Fatty liver; Kupffer cells; Lipid droplets; Lipid metabolism; Resveratrol