Abstract
Insulin resistance in skeletal muscle is one of the main features of metabolic syndrome, and it has been associated with lifestyle factors including diet 1) 2). Whereas the mechanisms underlying the development of insulin resistance have not been fully elucidated, the accumulation of intramyocellular lipid (IMCL) is recognized as an important determinant of insulin resistance, and is increased by a high-fat diet (HFD) 3) 4). The fat content of food is a determinant of the accumulation of IMCL. The effects of HFD on IMCL and insulin sensitivity are highly variable, although, it had shown that a short term (3-day) high-fat diet (HFD) in human increases the IMCL level and impairs insulin sensitivity in skeletal muscle 3) 5).
The aim of this study was to identify the genes in muscle that are related to this inter-individual variation.
Fifty non-obese healthy men were recruited for this study. Before and after HFD for 3 days, IMCL levels in the tibialis anterior were measured by 1H-magnetic resonance spectroscopy, and peripheral insulin sensitivity was evaluated by glucose infusion rate (GIR) during the euglycemic-hyperinsulinemic clamp. We observed a significant increase in TA-IMCL by HFD. GIR was significantly decreased by HFD. We also observed a negative correlation between changes in TA-IMCL and GIR by HFD (r=-0.37, p<0.01), Subjects who showed a large increase in IMCL and a large decrease in GIR by HFD were classified as the high-responder (HR), and the subjects who showed a small increase in IMCL and a small decrease in GIR were classified as the low-responder (LR). In 5 subjects in each group, the gene expression profile of the vastus lateralis muscle was analyzed by DNA microarray analyses. Before HFD, gene expression profiles related to lipid metabolism were comparable between the 2 groups. Gene Set Enrichment Analysis demonstrated that 5 gene sets related to lipid metabolism were up-regulated by HFD in the HR group, but not in the LR group. Changes in gene expression patterns were confirmed by qRT-PCR using more samples (LR: n=9; HR: n=11). These results suggest that IMCL accumulation/impaired insulin sensitivity after HFD is closely associated with changes in the expression of genes related to lipid metabolism in muscle.
© 2016 The Juntendo Medical Society. This is an open access article distributed under the terms of Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original source is properly credited.
