Dietary Macronutrient Composition Determines the Contribution of DGAT1 to Alcoholic Steatosis
| Autor: | Caleb T. Epps, Seung-Ah Lee, Ira J. Goldberg, Amit Saha, Sarahjean Kerolle, Yungying Hu, Li-Shin Huang, Robin D. Clugston, Jason J. Yuen, Hongfeng Jiang, William S. Blaner, Michael J. Trites |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Alcoholic liver disease medicine.medical_specialty Steatosis Liquid diet Medicine (miscellaneous) Context (language use) Alcohol Toxicology Triglyceride Gene Expression Regulation Enzymologic DGAT Mice 03 medical and health sciences chemistry.chemical_compound Internal medicine medicine Animals Diacylglycerol O-Acyltransferase Diet Fat-Restricted Triglycerides Diacylglycerol kinase Mice Knockout Nutrients Metabolism Lipid Metabolism medicine.disease Dietary Fats Diet Mice Inbred C57BL Psychiatry and Mental health 030104 developmental biology Endocrinology Liver chemistry Original Article Fatty Liver Alcoholic Biochemistry Pharmacology Physiology and Metabolism |
| Zdroj: | Alcoholism, Clinical and Experimental Research |
| ISSN: | 0145-6008 |
| DOI: | 10.1111/acer.13881 |
| Popis: | Background The first stage of alcoholic liver disease is hepatic steatosis. While alcohol is known to profoundly impact hepatic lipid metabolism, gaps in our knowledge remain regarding the mechanisms leading to alcohol‐induced hepatic triglyceride (TG) accumulation. As the sole enzymes catalyzing the final step in TG synthesis, diacylglycerol O‐acyltransferase (DGAT) 1 and 2 are potentially important contributors to alcoholic steatosis. Our goal was to study the effects of dietary fat content on alcohol‐induced hepatic TG accumulation, and the relative contribution of DGAT1 and DGAT2 to alcoholic steatosis. Methods These studies were carried out in wild‐type (WT) mice fed alcohol‐containing high‐fat or low‐fat formulations of Lieber‐DeCarli liquid diets, as well as follow‐up studies in Dgat1 −/− mice. Results A direct comparison of the low‐fat and high‐fat liquid diet in WT mice revealed surprisingly similar levels of alcoholic steatosis, although there were underlying differences in the pattern of hepatic lipid accumulation and expression of genes involved in hepatic lipid metabolism. Follow‐up studies in Dgat1 −/− mice revealed that these animals are protected from alcoholic steatosis when consumed as part of a high‐fat diet, but not a low‐fat diet. Conclusions Dietary macronutrient composition influences the relative contribution of DGAT1 and DGAT2 to alcoholic steatosis, such that in the context of alcohol and a high‐fat diet, DGAT1 predominates. |
| Databáze: | OpenAIRE |
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