Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet.
The accumulation of intramyocellular lipid (IMCL) is recognized as an important determinant of insulin resistance, and is increased by a high-fat diet (HFD). However, the effects of HFD on IMCL and insulin sensitivity are highly variable. The aim of this study was to identify the genes in muscle that are related to this inter-individual variation. Fifty healthy men were recruited for this study. Before and after HFD for 3 days, IMCL levels in the tibialis anterior were measured by (1)H magnetic resonance spectroscopy, and peripheral insulin sensitivity was evaluated by glucose infusion rate (GIR) during the euglycemic-hyperinsulinemic clamp. Subjects who showed a large increase in IMCL and a large decrease in GIR by HFD were classified as high responders (HRs), and subjects who showed a small increase in IMCL and a small decrease in GIR were classified as low responders (LRs). In five subjects from each group, the gene expression profile of the vastus lateralis muscle was analyzed by DNA microarray analysis. Before HFD, gene expression profiles related to lipid metabolism were comparable between the two groups. Gene Set Enrichment Analysis demonstrated that five gene sets related to lipid metabolism were upregulated 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.
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Saori
S
Kakehi
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; ys-tamur@juntendo.ac.jp.
Yoshifumi
Y
Tamura
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Kageumi
K
Takeno
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Yuko
Y
Sakurai
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Minako
M
Kawaguchi
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Takahiro
T
Watanabe
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Takashi
T
Funayama
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Fumihiko
F
Sato
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Shin-Ichi
S
Ikeda
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Akio
A
Kanazawa
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Yoshio
Y
Fujitani
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan;
Ryuzo
R
Kawamori
Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo, Japan; Center for Therapeutic Innovations in Diabetes, Juntendo University Graduate School of Medicine, Tokyo, Japan; and Center for Molecular Diabetology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Hirotaka
H
Watada
D000328:Adult; D056915:DNA Copy Number Variations / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
D004272:DNA, Mitochondrial; D004041:Dietary Fats
high-fat diet; insulin sensitivity; intramyocellular lipid