PMID- 25813056 OWN - NLM STAT- MEDLINE DCOM- 20150812 LR - 20181113 IS - 1522-1547 (Electronic) IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 308 IP - 11 DP - 2015 Jun 1 TI - Kupffer cell depletion protects against the steatosis, but not the liver damage, induced by marginal-copper, high-fructose diet in male rats. PG - G934-45 LID - 10.1152/ajpgi.00285.2014 [doi] AB - 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. CI - Copyright (c) 2015 the American Physiological Society. FAU - Song, Ming AU - Song M AD - Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville School of Medicine, Louisville, Kentucky; m0song03@louisville.edu. FAU - Schuschke, Dale A AU - Schuschke DA AD - Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky; FAU - Zhou, Zhanxiang AU - Zhou Z AD - 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. FAU - Zhong, Wei AU - Zhong W AD - Center for Translational Biomedical Research, University of North Carolina at Greensboro, Kannapolis, North Carolina; FAU - Zhang, Jiayuan AU - Zhang J AD - Department of Chemistry, University of Louisville School of Medicine, Louisville, Kentucky; FAU - Zhang, Xiang AU - Zhang X AD - Department of Pharmacology and Toxicology, Department of Chemistry, University of Louisville School of Medicine, Louisville, Kentucky; FAU - Wang, Yuhua AU - Wang Y AD - College of Food Science and Engineering, Jilin Agricultural University, Changchun, China. FAU - McClain, Craig J AU - McClain CJ AD - 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; LA - eng GR - U01 AA021901/AA/NIAAA NIH HHS/United States GR - DK-055030/DK/NIDDK NIH HHS/United States GR - R01AA015970/AA/NIAAA NIH HHS/United States GR - R01 AA014623/AA/NIAAA NIH HHS/United States GR - P01 AA017103/AA/NIAAA NIH HHS/United States GR - P01AA017103/AA/NIAAA NIH HHS/United States GR - R01 AA018869/AA/NIAAA NIH HHS/United States GR - R01 AA018844/AA/NIAAA NIH HHS/United States GR - R01DK071765/DK/NIDDK NIH HHS/United States GR - R01 DK071765/DK/NIDDK NIH HHS/United States GR - RC2 AA019385/AA/NIAAA NIH HHS/United States GR - P30AA019360/AA/NIAAA NIH HHS/United States GR - R01AA016013/AA/NIAAA NIH HHS/United States GR - P30 AA019360/AA/NIAAA NIH HHS/United States GR - R37AA010762/AA/NIAAA NIH HHS/United States GR - R01AA014623/AA/NIAAA NIH HHS/United States GR - R01 AA023681/AA/NIAAA NIH HHS/United States GR - R01 AA015970/AA/NIAAA NIH HHS/United States GR - R01 AA016013/AA/NIAAA NIH HHS/United States GR - R01AA018844/AA/NIAAA NIH HHS/United States GR - R01AA018869/AA/NIAAA NIH HHS/United States GR - R37 AA010762/AA/NIAAA NIH HHS/United States GR - R01 DK055030/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20150326 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Cytokines) RN - 0 (Srebf1 protein, rat) RN - 0 (Sterol Regulatory Element Binding Protein 1) RN - 30237-26-4 (Fructose) RN - 789U1901C5 (Copper) RN - AU0V1LM3JT (Gadolinium) RN - E1UOL152H7 (Iron) RN - P7082WY76D (gadolinium chloride) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology MH - *Chemical and Drug Induced Liver Injury/etiology/metabolism/prevention & control MH - Chemokine CCL2/metabolism MH - *Copper/deficiency/metabolism MH - Cytokines/metabolism MH - Diet/adverse effects/methods MH - *Fatty Liver/etiology/metabolism/prevention & control MH - *Fructose/administration & dosage/adverse effects/metabolism MH - Gadolinium/*pharmacology MH - Iron/metabolism MH - *Kupffer Cells/drug effects/physiology MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Sterol Regulatory Element Binding Protein 1/metabolism PMC - PMC4451322 OTO - NOTNLM OT - Kupffer cell OT - adipose tissue OT - copper OT - fructose OT - iron EDAT- 2015/03/31 06:00 MHDA- 2015/08/13 06:00 PMCR- 2016/06/01 CRDT- 2015/03/28 06:00 PHST- 2014/08/01 00:00 [received] PHST- 2015/03/24 00:00 [accepted] PHST- 2015/03/28 06:00 [entrez] PHST- 2015/03/31 06:00 [pubmed] PHST- 2015/08/13 06:00 [medline] PHST- 2016/06/01 00:00 [pmc-release] AID - ajpgi.00285.2014 [pii] AID - GI-00285-2014 [pii] AID - 10.1152/ajpgi.00285.2014 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2015 Jun 1;308(11):G934-45. doi: 10.1152/ajpgi.00285.2014. Epub 2015 Mar 26.