Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited

Abstract

Dubé JJ, Amati F, Stefanovic-Racic M, Toledo FG, Sauers SE, Goodpaster BH. Exercise-induced alterations in intramyocellular lipids and insulin resistance: the athlete's paradox revisited. Am J Physiol Endocrinol Metab 294: E882-E888, 2008. First published March 4, 2008 doi:10.1152/ajpendo.00769.2007.-We previously reported an "athlete's paradox" in which endurance-trained athletes, who possess a high oxidative capacity and enhanced insulin sensitivity, also have higher intramyocellular lipid (IMCL) content. The purpose of this study was to determine whether moderate exercise training would increase IMCL, oxidative capacity of muscle, and insulin sensitivity in previously sedentary overweight to obese, insulin-resistant, older subjects. Twenty-five older (66.4 Ϯ 0.8 yr) obese (BMI ϭ 30.3 Ϯ 0.7 kg/m 2 ) men (n ϭ 9) and women (n ϭ 16) completed a 16-wk moderate but progressive exercise training program. Body weight and fat mass modestly but significantly (P Ͻ 0.01) decreased. Insulin sensitivity, measured using the euglycemic hyperinsulinemic clamp, was increased (21%, P ϭ 0.02), with modest improvements (7%, P ϭ 0.04) in aerobic fitness (V O2peak). Histochemical analyses of IMCL (Oil Red O staining), oxidative capacity [succinate dehydrogenase activity (SDH)], glycogen content, capillary density, and fiber type were performed on skeletal muscle biopsies. Exercise training increased IMCL by 21%. In contrast, diacylglycerol and ceramide, measured by mass spectroscopy, were decreased (n ϭ 13; Ϫ29% and Ϫ24%, respectively, P Ͻ 0.05) with exercise training. SDH (19%), glycogen content (15%), capillary density (7%), and the percentage of type I slow oxidative fibers (from 50.8 to 55.7%), all P Յ 0.05, were increased after exercise. In summary, these results extend the athlete's paradox by demonstrating that chronic exercise in overweight to obese older adults improves insulin sensitivity in conjunction with favorable alterations in lipid partitioning and an enhanced oxidative capacity within muscle. Therefore, several key deleterious effects of aging and/or obesity on the metabolic profile of skeletal muscle can be reversed with only moderate increases in physical activity. insulin sensitivity; aging; diacylglycerol; ceramide SEVERAL STUDIES have demonstrated strong associations between high intramyocellular lipid (IMCL) content and skeletal muscle insulin resistance in obesity (25, 44), aging (11, 42, 45, 52), and type 2 diabetes (T2DM) (31,36, 58). Yet, despite these numerous observations, we (23) described an "athlete's paradox" that has since been confirmed by others (54, 58) in which highly insulin-sensitive, endurance-trained athletes have IMCL content similar to that observed in insulin-resistant obese and T2DM subjects. We (46) later reported that the exercise training-induced increase in IMCL was not limited to young, lean, highly trained athletes; in a group of older (ϳ67 yr), nonobese subjects, moderate aerobic exercise training increased IMCL content concomitant with improved oxidative capacity and overall ...

Subcellular lipid droplet distribution in red and white muscles in the obese Zucker rat

“…This view is supported by a number of observations, including the observation that overabundance of DGAT1 increases intramuscular triacylglycerol content, while protecting against diet-induced insulin resistance [33], as well as the finding that exercise-trained athletes display high intramuscular triacylglycerol content, but are highly insulin-sensitive [34,35]. However, a recent report by Nielsen and colleagues [5] suggests that triacylglycerol lipid droplets can negatively affect insulin signalling if accumulated in the subsarcolemmal subcellular region, thus renewing interest in triacylglycerol accumulation as a potential cause of insulin resistance.…”

Physically active vs. inactive lifestyle, muscle properties, and glucose homeostasis in middle-aged and older twins

“…Hb A1C , which is the measure of long-term plasma glucose concentration, is one of the mediating factors by which exercise decreases the risk for cardiovascular events (Thomas et al 2006;Mora et al 2007;Church et al 2010). However, the link between the intramuscular lipid accumulation and insulin resistance is not yet fully understood (Goodpaster et al 2001;Goodpaster and Brown 2005;Dube et al 2008;Hawley and Lessard 2008;Taube et al 2009;Eckardt et al 2011). One of the suggestions for the association could be the reduced aerobic capacity among the inactive co-twins (Leskinen et al 2010).…”

“…As such, the accumulation of ectopic "high-risk" fat and adipocyte function are important mechanisms in mediating the prolonged effects of life-long regular exercise on glucose metabolism (Goodpaster et al 2000;Boule et al 2005;Petersen and Shulman 2006;Dube et al 2008;Leskinen et al 2009b;Taube et al 2009;Rector and Thyfault 2011). Notably, the cotwins did not differ significantly in either body weight or BMI (see Table 1), and there were no differences in their fat intakes (Rintala et al 2011), yet the inactive co-twins had significantly more visceral, intramuscular, and liver fat, as we have reported earlier (Leskinen et al 2009b).…”

Physical Activity and Abnormal Blood Glucose Among Healthy Weight Adults

“…However, regardless of differences in diet and the genetic component of prediabetes and Type 2 diabetes, physical activity has been shown to elicit positive physiologic changes in blood glucose levels and insulin sensitivity. 37,38 Another limitation is that it is possible that people with abnormal blood glucose might be sicker and thus less likely to engage in physical activity. However, a lack of physical activity has been shown to contribute to unhealthy blood glucose levels.…”