Differential hepatotoxicity of dietary and DNL-derived palmitate in the methionine-choline-deficient model of steatohepatitis

BMC Gastroenterology

Research Article

Kevin Siao¹  Andrew A. Pierce¹  Jacquelyn J. Maher¹  James P. Grenert²  Michael K. Pickens³ 

[1] Liver Center Laboratory, San Francisco General Hospital, University of California San Francisco, 1001 Potrero Avenue, Building 40, Room 4102, 94110, San Francisco, CA, USA;Department of Medicine, University of California San Francisco, San Francisco, USA;Liver Center Laboratory, San Francisco General Hospital, University of California San Francisco, 1001 Potrero Avenue, Building 40, Room 4102, 94110, San Francisco, CA, USA;Department of Pathology, University of California San Francisco, San Francisco, USA;Liver Center Laboratory, San Francisco General Hospital, University of California San Francisco, 1001 Potrero Avenue, Building 40, Room 4102, 94110, San Francisco, CA, USA;Department of Pediatrics, University of California San Francisco, San Francisco, USA;Present address: Mary Bridge Children’s Health Center, 311 S. L Street, 98405, Tacoma, WA, USA;

关键词: Liver;    Fatty liver;    Lipotoxicity;    Saturated fat;    De novo lipogenesis;    Macronutrient;   

DOI  :  10.1186/s12876-015-0298-y

 received in 2015-02-03, accepted in 2015-06-05,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundSaturated fatty acids are toxic to liver cells and are believed to play a central role in the pathogenesis of non-alcoholic steatohepatitis. In experimental steatohepatitis induced by feeding mice a methionine-choline-deficient (MCD) diet, the degree of liver damage is related to dietary sugar content, which drives de novo lipogenesis and promotes the hepatic accumulation of saturated fatty acids. The objective of this study was to determine whether dietary palmitate exerts the same toxicity as carbohydrate-derived palmitate in the MCD model of fatty liver disease.MethodsWe fed mice custom MCS and MCD formulas containing 4 different carbohydrate-fat combinations: starch-oleate, starch-palmitate, sucrose-oleate and sucrose-palmitate.  After 3 wk, we compared their metabolic and disease outcomes.ResultsMice fed the custom MCD formulas developed varying degrees of hepatic steatosis and steatohepatitis, in the order starch-oleate < starch-palmitate < sucrose-oleate < sucrose-palmitate. Liver injury correlated positively with the degree of hepatic lipid accumulation. Liver injury also correlated positively with the amount of palmitate in the liver, but the relationship was weak. Importantly, mice fed MCD starch-palmitate accumulated as much hepatic palmitate as mice fed MCD sucrose-oleate, yet their degree of liver injury was much lower. By contrast, mice fed MCD sucrose-palmitate developed severe liver injury, worse than that predicted by an additive influence of the two nutrients.ConclusionIn the MCD model of steatohepatitis, carbohydrate-derived palmitate in the liver is more hepatotoxic than dietary palmitate. Dietary palmitate becomes toxic when combined with dietary sugar in the MCD model, presumably by enhancing hepatic de novo lipogenesis.

【 授权许可】

Unknown   
© Pierce et al. 2015. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.