Association Between Expression of FABPpm in Skeletal Muscle and Insulin Sensitivity in Intramyocellular Lipid-Accumulated Nonobese Men

Kawaguchi, Minako; Tamura, Yasuaki; Kakehi, Saori; Takeno, Kageumi; Sakurai, Yuko; Watanabe, Takahiro; Fukushima, Takashi; Sato, Fumihiko; Ikeda, Shin‐ichi; Ogura, Yuji; Saga, Norio; Naito, Hisashi; Fujitani, Yoshio; Kanazawa, Akio; Kawamori, Ryuzo; Watada, Hirotaka

doi:10.1210/jc.2014-1896

Cited by 20 publications

(25 citation statements)

References 36 publications

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“…Because fatty acids work as ligands for the PPARs and increase the expression levels of genes involved in fatty acid metabolism (10,13,23), it was hypothesized that the increased availability of fatty acids induces an increase in the capacity of muscle to oxidize fat, at least in part through their transcriptional response (10,13,15,22,23). This response is reasonable for the adaptation of muscle to dietary fat and for an increase in its ability to metabolize and gain energy.…”

Section: Discussionmentioning

confidence: 99%

“…samples were immediately placed in the RNA-stabilizing reagent RNAlater (Qiagen, Hilden, Germany) and stored at Ϫ80°C. Extraction of total RNA and DNA from the muscle samples was performed as previously described (15). Biochemical analyses of serum samples and total body fat content were analyzed as described previously (31).…”

Section: Methodsmentioning

confidence: 99%

“…To confirm the findings of the microarray results, gene expression levels were examined by real-time quantitative RT-PCR (qRT-PCR) in 9 subjects in the LR group and 11 subjects in the HR group, as previously described (15). Primers were designed using Primer-Blast (National Center for Biotechnology Information).…”

Section: Methodsmentioning

confidence: 99%

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Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet

Kakehi

Tamura

Takeno

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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. Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet. Am J Physiol Endocrinol Metab 310: E32-E40, 2016. First published October 20, 2015 doi:10.1152/ajpendo.00220.2015.-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 ϭ 9; HR, n ϭ 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. intramyocellular lipid; insulin sensitivity; high-fat diet

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet

Kakehi

Tamura

Takeno

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…Overexpression of FABPpm in culture myocytes increased fatty acid oxidation coupled with the elevated expression of genes related to fatty acid oxidation. These results suggest that the level of FABPpm expression may play an important role in insulin sensitivity in the fat accumulated muscle 13) ( Figure-4).…”

Section: Sportology Center Core Studymentioning

confidence: 78%

Etiology of Insulin Resistance in Asian Non-Obese Subjects -Juntendo Sportology Center Core Study-

Watada

2016

Juntendo Medical Journal

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Obesity and its associated metabolic disorders are rapidly disseminating all over the world. While they became serious health problem, such diseases in Asians shows different features from those in other races such as Caucasian and African. One of the important features is a susceptibility to develop to type 2 diabetes even without excess body mass index. To search for the mechanism underlying this feature is important to find the suitable therapeutic strategy for Asian obesity. Thus, as a core study of the Sportology Center of Juntendo University Graduate School of Medicine, we assessed tissue-specific insulin resistance in Japanese non-obese subjects. In this study, we recruited non-obese and non-diabetic Japanese subjects and measured insulin sensitivity in muscle and liver by a 2-step hyperinsulinemiceuglycemic clamp with glucose tracer and ectopic fat content in muscle and liver by proton magnetic resonance spectroscopy. So far, our data suggests that muscle insulin resistance may play a central role in future onset of the diseases that could make the healthy people to disable people.

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“…Recently, we have shown the possibility that differences in the gene expression of fatty acid transporters lead to differences in insulin sensitivity and oxidative capacity in IMCL-accumulated subjects 22) . We recruited 36 non-obese healthy men and compared gene expression levels in the vastus lateralis muscle between IMCL-accumulated high insulin sensitivity subjects (H-GIR, n = 8) and low insulin sensitivity subjects (L-GIR, n = 9).…”

Section: Athlete's Paradox Phenomenonmentioning

confidence: 99%

Intracellular lipid accumulation and insulin sensitivity in muscle and liver: Fighting against “intracellular obesity”

Tamura

Kakehi

Takeno

2014

JPFSM

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Insulin resistance induced by obesity is important in the pathogenesis of metabolic syndrome and type 2 diabetes. On the other hand, recent data suggest that ectopic fat accumulation in muscle and liver induces insulin resistance in these organs, independent of obesity. For example, short-term calorie restriction greatly decreased intrahepatic lipid levels and improved hepatic glucose metabolism in patients with metabolic disease. In addition, short-term aerobic exercise decreased intramyocellular lipid accumulation and improved insulin resistance in skeletal muscle. Similarly, physical inactivity was identified as a risk factor of intramyocellular lipid accumulation during a 3-day high fat diet. Considering the fact that metabolic diseases are frequently observed in lean subjects in East Asian countries, ectopic fat accumulation in insulin target organs may be an important pathogenesis of, as well as a therapeutic target of, metabolic diseases in non-obese subjects. Thus, it may be more appropriate to call fat accumulation in insulin target organs as "intracellular obesity" rather than ectopic fat. Furthermore, it is important to perform additional research to clarify the pathogenesis of metabolic diseases in non-obese subjects.

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Association Between Expression of FABPpm in Skeletal Muscle and Insulin Sensitivity in Intramyocellular Lipid-Accumulated Nonobese Men

Abstract: Differences in the gene expression of fatty acid transporters may, at least in part, affect insulin sensitivity in IMCL-accumulated nonobese men.

Cited by 20 publications

References 36 publications

Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet

Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high-fat diet

Etiology of Insulin Resistance in Asian Non-Obese Subjects -Juntendo Sportology Center Core Study-

Intracellular lipid accumulation and insulin sensitivity in muscle and liver: Fighting against “intracellular obesity”

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