Skeletal muscle lipid accumulation in obesity, insulin resistance, and type 2 diabetes

Abstract

In addition to obesity, many factors, including the distribution of body fat, contribute to the development of insulin resistance and type 2 diabetes mellitus (T2DM). Lipid contained within skeletal muscle as triglyceride is a parameter of regional fat accumulation thought to be an important link among obesity, insulin resistance, and type 2 diabetes, even in the pediatric population. Intramuscular triglycerides can also be a fuel source for healthy muscle during periods of physical activity. Thus, the balance between storage and efficient utilization of muscle triglycerides is likely a key to a better understanding of the interaction between dysregulated fat and glucose metabolism by muscle in both adults and children. This review examines the evidence that muscle lipid accumulation is linked with insulin resistance and type 2 diabetes of both adults and children. In addition, we explore the potential mechanisms for muscle lipid accumulation as well as the effects of weight loss and physical activity on muscle lipid. Further defining the links between muscle lipid accumulation and insulin action should help develop more effective strategies to prevent or treat type 2 diabetes and other obesity-associated disorders.

Non-invasive assessment of lower extremity muscle composition after incomplete spinal cord injury

“…4 Although IMCL is purportedly influenced by diet and exercise; studies also report strong correlations between IMCL and insulin resistance irrespective of diet, age, weight, activity level and gender. 5 Nevertheless, in our study, while gender, body weight, physical activity and age were well controlled, elevations in myocellular lipids (3.3 (IMCL) and 4.5 (EMCL) times elevation relative to controls) are far greater than those attributable to dietary influences (0.32 times elevation in previous dietary studies). 4 The highly elevated IMCL levels in the incomplete SCI group in this study raises concern because of their reported association with insulin resistance in sedentary individuals with normal body weights as well as obese individuals.…”

“…6 Moreover, skeletal muscle is the major depot (B80%) for blood glucose and marked muscle atrophy has been shown to be a secondary risk factor for insulin resistance. 5 The combination of muscle atrophy, 1 relative inactivity 8 and high IMCL levels in persons with incomplete SCI potentially renders this patient population particularly vulnerable to altered glucose homeostasis. Accordingly, in the light of recognizing elevated IMCL content as detected by MR measures, our findings suggest that such metabolic adaptations should be assessed in response to the injury as well as different rehabilitation protocols in this patient cohort.…”

“…Glucose intolerance and insulin resistance are purported as two of the major metabolic risk factors in the development of cardiovascular complications after SCI. 3 Strong evidence in the literature suggests obvious positive correlations between intramyocellular lipid (IMCL) and insulin resistance in individuals with a relatively sedentary lifestyle including healthy individuals, 4 elderly 5 and persons with obesity. 5,6 Accordingly, IMCL depots in skeletal muscle may provide an indirect measure of insulin resistance.…”

“…3 Strong evidence in the literature suggests obvious positive correlations between intramyocellular lipid (IMCL) and insulin resistance in individuals with a relatively sedentary lifestyle including healthy individuals, 4 elderly 5 and persons with obesity. 5,6 Accordingly, IMCL depots in skeletal muscle may provide an indirect measure of insulin resistance. Given the higher reported incidence of insulin resistance in persons with incomplete SCI 7 and a purported relatively inactive lifestyle, 8 we hypothesized that individuals with incomplete SCI would demonstrate an elevated IMCL content in skeletal muscle.…”

Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome

“…9 IMCL content is determined by the balance between the uptake of free fatty acid into skeletal muscle cells and fatty acid b-oxidation within the mitochondria. 10 Thus, abnormal fatty acid metabolism within the mitochondria can reduce the production of energy from fatty acid, which in turn might impair aerobic capacity in MetS. However, the significance of IMCL in the skeletal muscle energy metabolism and aerobic capacity in MetS is not fully elucidated.…”