title: Kupffer cell depletion protects against the steatosis, but not the liver damage, induced by marginal-copper, high-fructose diet in male rats.
abstract: High-fructose feeding impairs copper status and leads to low copper availability, which is a novel mechanism in obesity-related fatty liver. Copper deficiency-associated hepatic iron overload likely plays an important role in fructose-induced liver injury. Excess iron in the liver is distributed throughout hepatocytes and Kupffer cells (KCs). The aim of this study was to examine the role of KCs in the pathogenesis of nonalcoholic fatty liver disease induced by a marginal-copper high-fructose diet (CuMF). Male weanling Sprague-Dawley rats were fed either a copper-adequate or a marginally copper-deficient diet for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was also given ad libitum. KCs were depleted by intravenous administration of gadolinium chloride (GdCl3) before and/or in the middle of the experimental period. Hepatic triglyceride accumulation was completely eliminated with KC depletion in CuMF consumption rats, which was associated with the normalization of elevated plasma monocyte chemoattractant protein-1 (MCP-1) and increased hepatic sterol regulatory element binding protein-1 expression. However, hepatic copper and iron content were not significantly affected by KC depletion. In addition, KC depletion reduced body weight and epididymal fat weight as well as adipocyte size. Plasma endotoxin and gut permeability were markedly increased in CuMF rats. Moreover, MCP-1 was robustly increased in the culture medium when isolated KCs from CuMF rats were treated with LPS. Our data suggest that KCs play a critical role in the development of hepatic steatosis induced by marginal-copper high-fructose diet.
authors: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, Kentucky; m0song03@louisville.edu.
authors: Ming
authors: M
authors: Song
authors: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky;
authors: Dale A
authors: DA
authors: Schuschke
authors: Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina; Department of Nutrition, University of North Carolina at Greensboro, Kannapolis, North Carolina; and.
authors: Zhanxiang
authors: Z
authors: Zhou
authors: Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina;
authors: Wei
authors: W
authors: Zhong
authors: Department of Chemistry, University of Louisville School of Medicine, Louisville, Kentucky;
authors: Jiayuan
authors: J
authors: Zhang
authors: Department of Pharmacology and Toxicology, Department of Chemistry, University of Louisville School of Medicine, Louisville, Kentucky;
authors: Xiang
authors: X
authors: Zhang
authors: College of Food Science and Engineering, Jilin Agricultural University, Changchun, China.
authors: Yuhua
authors: Y
authors: Wang
authors: Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, Kentucky; Department of Pharmacology and Toxicology, Robley Rex Veterans Affairs Medical Center, Louisville, Kentucky;
authors: Craig J
authors: CJ
authors: McClain
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D018932:Chemokine CCL2 / Q000378:metabolism; D003300:Copper / Q000172:deficiency / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004032:Diet / Q000009:adverse effects / Q000379:methods; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D016207:Cytokines; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D005632:Fructose; D003300:Copper; D005682:Gadolinium; D007501:Iron; C038958:gadolinium chloride
keywords: Kupffer cell; adipose tissue; copper; fructose; iron