A high fat diet with a high C18:0/C16:0 ratio induced worse metabolic and transcriptomic profiles in C57BL/6 mice

Abstract

Background: Differential effects of individual saturated fatty acids (SFAs), particularly stearic acid (C18:0) relative to the shorter-chain SFAs have drawn an interest for more accurate nutritional guidelines. But specific biologic and pathologic functions that can be assigned to particular SFAs are very limited. The present study was designed to compare changes in metabolic and transcriptomic profiles in mice caused by high C18:0 diet and high palmitic acid (C16:0) diet.Methods: Male C57BL/6 mice were assigned to a normal fat diet (NFD), a high fat diet with high C18:0 / C16:0 ratio (HSF) or an isocaloric high fat diet with a low C18:0 / C16:0 ratio (LSF) for 10 weeks. Oral glucose tolerance test, 72h-energy expenditure measurement and CT scan of body fat were done before sacrifice. Fasting glucose and lipids were determined by an auto-biochemical analyzer. Blood insulin, tumor necrosis factor-α (TNF-α)，and interleukin-6 (IL-6) were measured by enzyme linked immunosorbent assay methods. Free fatty acids (FFAs) profiles in blood and liver were determined by using Gas Chromatography-Mass Spectrometry. Microarray analysis was applied to investigate changes in transcriptomic profiles in liver. Pathway analysis and Gene Ontology analysis were applied to describe the roles of differentially expressed mRNAs. Results: Compared with NFD group, body weight, body fat ratio, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride, IL-6, serum and liver FFAs including total FFAs, C16:0 and C18:0 were increased in both high fat diet groups, which were much higher in HSF group than those in LSF group. Both HSF and LSF mice exhibited distinguishable lncRNA, microRNA and mRNA expression profiles, compared with NFD mice. And more differentially expressed lncRNAs and mRNAs were observed in HSF group than those in LSF group. Some biological functions and pathways, other than energy metabolism regulation, were identified that differentially expressed mRNAs between HSF group and LSF group probably involved in. Conclusion: The high fat diet with a high C18:0/C16:0 ratio induced much severe glucose and lipid metabolic disorders and inflammation, and affected more lncRNAs and mRNAs expression than an isocaloric low C18:0/C16:0 ratio diet in mice. These results provide new insights into the different biological functions and related mechanisms, other than glucose and lipid metabolism, between C16:0 and C18:0.Take home message: A high fat diet with a high C18:0/C16:0 ratio probably leads to more changes in multiple biological processes or signaling pathways at transcriptional level than an isocaloric low C18:0/C16:0 ratio diet. The ratio of C18:0/C16:0 in diets should be taken into account for accurate nutrition and health in future.