Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state

Abstract

Numerous studies have reported a strong correlation between intramuscular triacylglycerol (IMTG) content and insulin resistance. However, the proposed relationship between IMTG accumulation and skeletal muscle insulin resistance is not unambiguous, as trained athletes have been shown to be markedly insulin sensitive despite an elevated IMTG storage. Though the latter has often been attributed to differences in muscle fibre type composition and/or structural characteristics of the intramyocellular lipid deposits, recent studies have failed to provide such evidence. The greater insulin sensitivity despite an elevated IMTG deposition in the endurance-trained state has often been described as a metabolic paradox. However, divergent metabolic events are responsible for the greater IMTG content in the endurance-trained versus insulin-resistant states. The greater IMTG storage in the trained athlete represents an adaptive response to endurance training, allowing a greater contribution of the IMTG pool as a substrate source during exercise. In contrast, elevated IMTG stores in the obese and/or type 2 diabetes patient seem to be secondary to a structural imbalance between plasma free fatty acid availability, fatty acid (FA) storage and oxidation. Therefore, the reported correlation between IMTG content and insulin resistance does not represent a functional relationship, as it is strongly influenced by training status and/or habitual physical activity. It can be argued that the ratio between IMTG content and muscle oxidative capacity represents a more accurate marker of insulin resistance. Interventions to augment mitochondrial density and/or function are likely to improve the balance between FA uptake and oxidation and should be applied to prevent and/or treat insulin resistance.

Effect of exercise training on insulin sensitivity, mitochondria and computed tomography muscle attenuation in overweight women with and without polycystic ovary syndrome

“…Interaction between mitochondrial function and IMCL accumulation may be the important factor for determining insulin sensitivity [42]. The literature supports an association between skeletal muscle mitochondrial dysfunction, high adiposity and IR in people with obesity and type 2 diabetes and IR in first-degree relatives of those with type 2 diabetes, but controversy remains [19].…”

Long-standing, insulin-treated type 2 diabetes patients with complications respond well to short-term resistance and interval exercise training

“…Insulin resistance and visceral adiposity (41-43) as well as low cardiorespiratory fitness (39) have been associated with a state of chronic inflammation and ectopic fat accumulation in liver (40) and muscle (33) tissue. Therefore, in the present study, we investigated whether markers for systemic inflammation and lipid abnormalities would change following a short-term exercise intervention.…”

“…Previous studies have shown that changes in muscle fibre-type composition (20)(21)(22)(23), muscle oxidative capacity (MUOX) (24) and intramyocellular lipid (IMCL) (25,26) and/or glycogen (25) content are associated with the development of skeletal muscle insulin resistance. Although insulin sensitivity has been reported to improve following resistance (27)(28)(29) as well as endurance-type (2, 30-32) exercise training, the concomitant structural changes in resting IMCL and/or glycogen content following exercise interventions in T2D patients remain controversial (33)(34)(35)(36)(37)(38).…”

“…Over the past couple of years, it has been suggested that in the context of cardiorespiratory deconditioning (39) and ectopic fat accumulation (33,(40)(41)(42)(43), chronic low-grade inflammation plays an important role in the development of microvascular complications in the insulin-resistant state (44,45). Recent studies indicate that lifestyle interventions modulate circulating adipokine levels and reduce the level of systemic inflammation (46), thereby improving whole-body insulin sensitivity (47).…”

Increased susceptibility to oxidative damage in post-diabetic human myotubes

“…Ectopic accumulation of lipid in skeletal muscle (intramuscular triacylglycerol [IMTG]) is associated with obesity and highly correlated with the development of insulin resistance [6][7][8]. However, the observation that lean, insulin-sensitive endurance-trained athletes have high levels of IMTG has led to the hypothesis that altered or incomplete lipid metabolism may be an important factor in the progression of insulin resistance (reviewed by van Loon and Goodpaster [9]). Along these lines, it has been proposed that the overflow of triacylglycerol metabolites in skeletal muscle mitochondria leads to an uncoupling of the tricarboxylic acid cycle and the electron transport chain (ETC), resulting in an accumulation of incompletely oxidised long-chain fatty acids [10].…”