Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects

Recent evidence suggests that intramyocellular lipid (IMCL) accretion is associated with obesity and the development of insulin resistance and/or type 2 diabetes. However, trained endurance athletes are markedly insulin sensitive, despite an elevated mixed muscle lipid content. In an effort to explain this metabolic paradox, we compared muscle fiber type-specific IMCL storage between populations known to have elevated IMCL deposits. Immunofluorescence microscopy was performed on muscle biopsies obtained from eight highly trained endurance athletes, eight type 2 diabetes patients, and eight overweight, sedentary men after an overnight fast. Mixed muscle lipid content was substantially greater in the endurance athletes (4.0 ± 0.4% area lipid stained) compared with the diabetes patients and the overweight men (2.3 ± 0.4 and 2.2 ± 0.5%, respectively). More than 40% of the greater mixed muscle lipid content was attributed to a higher proportion type I muscle fibers (62 ± 8 vs. 38 ± 3 and 33 ± 7%, respectively), which contained 2.8 ± 0.3-fold more lipid than the type II fibers. The remaining difference was explained by a significantly greater IMCL content in the type I muscle fibers of the trained athletes. Differences in IMCL content between groups or fiber types were accounted for by differences in lipid droplet density, not lipid droplet size. IMCL distribution showed an exponential increase in lipid content from the central region toward the sarcolemma, which was similar between groups and fiber types. In conclusion, IMCL contents can be substantially greater in trained endurance athletes compared with overweight and/or type 2 diabetes patients. Because structural characteristics and intramyocellular distribution of lipid aggregates seem to be similar between groups, we conclude that elevated IMCL deposits are unlikely to be directly responsible for inducing insulin resistance.

Download Full-text

Increased intramyocellular lipid content but normal skeletal muscle mitochondrial oxidative capacity throughout the pathogenesis of type 2 diabetes

The FASEB Journal ◽

10.1096/fj.08-112318 ◽

2008 ◽

Vol 22 (11) ◽

pp. 3947-3955 ◽

Cited By ~ 61

Author(s):

Henk M. De Feyter ◽

Ellen Lenaers ◽

Sander M. Houten ◽

Patrick Schrauwen ◽

Matthijs K. Hesselink ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Lipid Content ◽

Oxidative Capacity ◽

Intramyocellular Lipid ◽

Mitochondrial Oxidative Capacity ◽

Intramyocellular Lipid Content

Download Full-text

Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects

Diabetologia ◽

10.1007/s00125-006-0475-1 ◽

2006 ◽

Vol 50 (1) ◽

pp. 113-120 ◽

Cited By ~ 173

Author(s):

V. B. Schrauwen-Hinderling ◽

M. E. Kooi ◽

M. K. C. Hesselink ◽

J. A. L. Jeneson ◽

W. H. Backes ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Lipid Content ◽

Mitochondrial Function ◽

Matched Control ◽

Intramyocellular Lipid ◽

Intramyocellular Lipid Content

Download Full-text

Effect of Dexamethasone on Glucose Tolerance and Fat Metabolism in a Diet-Induced Obesity Mouse Model

Endocrinology ◽

10.1210/en.2007-1214 ◽

2007 ◽

Vol 149 (2) ◽

pp. 758-766 ◽

Cited By ~ 52

Author(s):

John S. Gounarides ◽

Marion Korach-André ◽

Karen Killary ◽

Gregory Argentieri ◽

Oliver Turner ◽

...

Keyword(s):

Insulin Resistance ◽

Lipid Metabolism ◽

Glucose Tolerance ◽

Lipid Content ◽

Molecular Mechanisms ◽

Prolonged Exposure ◽

Tibialis Anterior Muscle ◽

Intramyocellular Lipid ◽

Diet Induced Obesity ◽

Intramyocellular Lipid Content

Prolonged exposure to elevated glucocorticoid levels is known to produce insulin resistance (IR), a hallmark of diabetes mellitus. Although not fully elucidated, the underlying molecular mechanisms by which glucocorticoids induce IR may provide potential targets for pharmacological interventions. Here we characterized muscle lipid metabolism in a dexamethasone-aggravated diet-induced obesity murine model of IR. Male C57BL/6 mice on a high-fat diet for 2 months when challenged with dexamethasone showed elevated food consumption and weight gain relative to age and diet-matched animals dosed with saline only. Dexamethasone treatment impaired glucose tolerance and significantly increased the intramyocellular lipid content in the tibialis anterior muscle (TA). A good correlation (r = 0.76, P < 0.01) was found between accumulation in intramyocellular lipid content in the TA and visceral adiposity. The linoleic acid (18:2) to polyunsaturated acid ratio was increased in the dexamethasone-treated animals (+29%; P < 0.01), suggesting a possible increase in stearoyl-CoA desaturase 2 activity, as reported in Sertoli cells. The treatment was also accompanied by a reduction in the percent fraction of ω-3 and long-chain polyunsaturated fatty acids in the TA. Analysis of the low-molecular-weight metabolites from muscle extracts showed that there was no dysregulation of muscle amino acids, as has been associated with dexamethasone-induced muscle proteolysis. In conclusion, dexamethasone-induced insulin resistance in diet-induced obese mice is associated with a profound perturbation of lipid metabolism. This is particularly true in the muscle, in which an increased uptake of circulating lipids along with a conversion into diabetogenic lipids can be observed.

Download Full-text

Effect of short-term exercise training on intramyocellular lipid content

Applied Physiology Nutrition and Metabolism ◽

10.1139/h2012-051 ◽

2012 ◽

Vol 37 (5) ◽

pp. 822-828 ◽

Cited By ~ 16

Author(s):

Sudip Bajpeyi ◽

Melissa A. Reed ◽

Sara Molskness ◽

Christopher Newton ◽

Charles J. Tanner ◽

...

Keyword(s):

Exercise Training ◽

Muscle Glycogen ◽

Periodic Acid ◽

Intramyocellular Lipid ◽

Periodic Acid Schiff ◽

Before And After ◽

Intramyocellular Lipid Content ◽

Type 2 Diabetic ◽

Oil Red O

The purpose of this study was to investigate the influence of exercise training on intramyocellular lipid (IMCL) content and test the hypothesis that the effect of endurance-oriented exercise training on IMCL is dependent on characteristics of the population studied. Lean (N = 11, body mass index (BMI) = 22.2 ± 0.7 kg·m–2), obese (N = 14, BMI = 38.8 ± 1.7 kg·m–2), and type 2 diabetic (N = 9, BMI = 35.5 ± 2.5 kg·m–2) participants were examined before and after 10 consecutive days of endurance-oriented (60 min·day–1 at ~70% [Formula: see text]O2peak) exercise training. IMCL and muscle glycogen were measured by Oil-Red-O and periodic acid – Schiff staining, respectively. The results indicated that IMCL was elevated (p < 0.05) in the obese and diabetic groups compared with the lean subjects prior to training. After training, IMCL content decreased (–35%) in the participants with type 2 diabetes; there were no changes in IMCL in the lean or obese groups. Muscle glycogen content was lower in the diabetic subjects than in the lean subjects both before and after training. These data indicate that changes in IMCL with exercise training do not exhibit a universal response but rather depend on the metabolic status of the population studied.

Download Full-text