Kahoko Nishikawa1, Keiichi Iwaya2, Manabu Kinoshita3, Yoko Fujiwara4, Mai Akao4, Mariko Sonoda4, Suresh Thiruppathi5, Takayoshi Suzuki5, Sadayuki Hiroi6, Shuhji Seki3, Toshihisa Sakamoto7. 1. Faculty of Commerce, Chuo University, Tokyo, Japan. 2. Department of Basic Pathology, National Defense Medical College, Saitama, Japan. 3. Department of Immunology and Microbiology, National Defense Medical College, Saitama, Japan. 4. Department of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan. 5. Division of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Japan. 6. Department of Laboratory Medicine, National Defense Medical College, Saitama, Japan. 7. Department of Traumatology and Critical Care Medicine, National Defense Medical College, Saitama, Japan.
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.
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.
Authors: Iñaki Milton-Laskibar; Leixuri Aguirre; Alfredo Fernández-Quintela; Anabela P Rolo; João Soeiro Teodoro; Carlos M Palmeira; María P Portillo Journal: Nutrients Date: 2017-07-11 Impact factor: 5.717