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 interest for more accurate nutritional guidelines. However, 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 a 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. An oral glucose tolerance test, 72-h energy expenditure measurement and CT scan of body fat were done before sacrifice. Fasting glucose and lipids were determined by an autobiochemical analyzer. Blood insulin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels 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 the liver. Pathway analysis and gene ontology analysis were applied to describe the roles of differentially expressed mRNAs. Results: Compared with the 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 and were much higher in the HSF group than those in the LSF group. Both HSF and LSF mice exhibited distinguishable long non-coding RNA (lncRNA), microRNA and mRNA expression profiles when compared with those of NFD mice. Additionally, more differentially expressed lncRNAs and mRNAs were observed in the HSF group than in the LSF group. Some biological functions and pathways, other than energy metabolism regulation, were identified as differentially expressed mRNAs between the HSF group and the LSF group.

LPGAT1 controls the stearate/palmitate ratio of phosphatidylethanolamine and phosphatidylcholine in sn-1 specific remodeling

“…The relative abundance of palmitate and stearate seems to be significant. Studies have demonstrated that either the genetic manipulation of the palmitate/stearate ratio in phospholipids ( 21 ) or the dietary alteration of the palmitate/stearate ratio ( 22 ) affect insulin resistance and body fat ratio. Thus, it seems likely that the palmitate/stearate ratio requires regulation.…”

Saturated fatty acid concentrations are predictive of insulin sensitivity and beta cell compensation in dogs

“…Of note, Kang et al demonstrate that increases in visceral adipose mass, not subcutaneous adipose mass, are associated with elevated fatty acid concentrations in humans 42 . Our analysis of fatty acid profiles in dogs revealed a significant elevation in fatty acid species that have been directly implicated in the deterioration of insulin sensitivity, such as palmitic and stearic acid 43 , 44 . Furthermore, HFD feeding elevated nearly all SFA species and associated 18:1 (oleic acid) and 18:2 (linoleic acid), while significantly reducing the abundance of DPA and DHA—2 fatty acids associated with improved insulin sensitivity 45 .…”

Endotoxin Tolerance Acquisition and Altered Hepatic Fatty Acid Profile in Aged Mice

“…Altered C18:C16 ratios and the expression of the fatty acid elongase ELOVL6 have been reported to contribute to NASH [ 28 , 43 , 44 ]. Depending on the mouse model, either elevated [ 28 ] or decreased [ 59 ] ratios have been observed, while human data indicate that reduced C18:C16 are found in steatohepatitis [ 60 ]. Interestingly, it has been shown that an age-associated upregulation of circulating C16:0 can promote pro-inflammatory monocyte polarization.…”