Kupffer cell depletion protects against the steatosis, but not the liver damage, 1 induced by marginal copper, high fructose diet in male rats, 2015 Mar 26, Am J Physiol Gastrointest Liver Physiol., Song M1, Schuschke DA2, Zhou Z3, Zhong W3, Zhang J2, Zhang X2, Wang Y2, McClain CJ2.
- 1University of Louisville firstname.lastname@example.org.
- 2University of Louisville.
- 3University of North Carolina at Greensboro.
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 (NAFLD) 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 weeks. Deionized water or deionized water containing 30% fructose (w/v) was also given ad lib. 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 (SREBP-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.
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