Hepatic Lipidomic Analysis of Dietary Different Type of Fats and Fructose Interactions in the Pathogenesis of Nonalcoholic Fatty Liver Diseases
FASEB J. 2022 May;36 Suppl 1. doi: 10.1096/fasebj.2022.36.S1.R3698.
ABSTRACT
OBJECTIVE: Dietary nutrient interactions are key determinants to the development of nonalcoholic fatty liver disease (NAFLD). Fat and fructose are two major components of Western diet. This study aimed to determine the combined effects of different type of dietary fats and fructose on the development of NAFLD in a murine model.
METHODS: Male adult C57BL/6J mice were assigned to six groups and fed with diets (AIN-93G based) enriched with different types of fat, such as saturated fat (SF-beef tallow), n-6 polyunsaturated fat (n6USF-corn oil), or n-3 polyunsaturated fat (n3USF-menhaden fish oil), respectively, with or without fructose supplementation through 10% fructose (w/v) in the drinking water ad lib for 20 weeks. 42% of calories was derived from the fat. Metabolic phenotypes were characterized by liver histology, plasma ALT and AST, glucose tolerance test, hepatic mRNA expression of genes involved in lipid metabolism, and lipidomic analysis of hepatic fatty acid composition.
RESULTS: While both SF and n6USF fed mice developed obesity and hepatic steatosis with or without fructose, SFA fed mice were characterized with hepatomegaly, liver injury and fibrosis, which were further exacerbated by fructose; conversely, plasma triglyceride levels were lower compared to controls. Interestingly, n6USF fed mice exhibited steatosis without hepatomegaly, and this was associated with markedly elevated plasma triglyceride and free fatty acid levels, which were blunted by fructose. Moreover, fructose and n6USF led to markedly elevated glucose intolerance tests compared to controls. Hepatic lipidomic analysis revealed that total monounsaturated fatty acids, but not total SFA, exhibited a stepwise decrease from SF to n6USF and n3USF fed mice across most of the lipid pools, which parallels the hepatic triglyceride content, irrespective the presence of fructose. In line with this, hepatic mRNA levels of lipogenesis genes, including Srebf1, Scd1, Fasn, Acacaand Acacb, displayed a similar pattern of alterations (SF>n6USF>n3USF), suggesting that increased lipogenesis contributes to hepatic steatosis in SF and n6USF fed mice. Of note, fructose play a mild, but significant role in the alterations of specific individual fatty acids in certain fatty acid pools, despite the predominant role played by the dietary fats.
CONCLUSION: Our data suggest that excess energy from SF intake results in fat storage in the liver, likely due to impaired triglyceride secretion; whereas excess energy from n6USF intake is stored in the periphery. Both effects were exacerbated by fructose supplementation. n3USF is beneficial even in the presence of fructose.
PMID:35553989 | DOI:10.1096/fasebj.2022.36.S1.R3698