Author:
Adar Tomer,Ben Ya’acov Ami,Shabat Yehudit,Mizrahi Meir,Zolotarov Lida,Lichtenstein Yoav,Ilan Yaron
Abstract
Abstract
Introduction
Glucocorticoids contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Natural killer T cells play a role in the pathogenesis of NAFLD and response to steroids. The present study aimed to determine the role of CD1d in steroid-mediated metabolic derangement and the steroid-protective effect of glycosphingolipids.
Methods
Ten groups of mice were studied. Steroids were orally administered to C57BL/6 mice to assess the therapeutic effect of β-glucosylceramide (GC) on the development of steroid-mediated liver damage and metabolic derangements. The role of CD1d in the pathogenesis of steroid-induced liver damage and in mediating the hepatoprotective effect of GC was studied in CD1d−/− mice.
Results
A model of oral administration of steroids was established, resulting in insulin resistance, hyperinsulinemia, hypertriglyceridemia, liver steatosis, and hepatocellular injury. Steroid administration to CD1d−/− mice was associated with hyperglycemia and hypertriglyceridemia. However, CD1d−/− mice did not manifest marked steroid-induced steatosis. GC treatment alleviated steroid-associated metabolic derangements and liver injury independent of CD1d expression.
Conclusion
A steroid-mediated model of NAFLD and metabolic derangements was established in which steroid-mediated steatosis was CD1d-dependent while steroid-induced liver necrosis, inflammation, and metabolic changes were CD1d-independent, which may support a dichotomy between steatosis and steatohepatitis in NAFLD.
Publisher
Springer Science and Business Media LLC
Subject
Gastroenterology,General Medicine
Reference56 articles.
1. Letteron P, Brahimi-Bourouina N, Robin MA, et al. Glucocorticoids inhibit mitochondrial matrix acyl-CoA dehydrogenases and fatty acid beta-oxidation. Am J Physiol. 1997;272:G1141–50.
2. Jia Y, Viswakarma N, Fu T, et al. Conditional ablation of mediator subunit MED1 (MED1/PPARBP) gene in mouse liver attenuates glucocorticoid receptor agonist dexamethasone-induced hepatic steatosis. Gene Expr. 2009;14:291–306.
3. Manmontri B, Sariahmetoglu M, Donkor J, et al. Glucocorticoids and cyclic AMP selectively increase hepatic lipin-1 expression, and insulin acts antagonistically. J Lipid Res. 2008;49:1056–67.
4. Peckett AJ, Wright DC, Riddell MC. The effects of glucocorticoids on adipose tissue lipid metabolism. Metabolism. 2011;60:1500–10.
5. Macfarlane DP, Forbes S, Walker BR. Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome. J Endocrinol. 2008;197:189–204.
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献