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

Department of Movement Sciences, Nutrition Research Institute Maastricht, Maastricht University, 616, 6200, Maastricht, MD, The Netherlands,
Pflügers Archiv - European Journal of Physiology (Impact Factor: 4.1). 03/2006; 451(5):606-16. DOI: 10.1007/s00424-005-1509-0
Source: PubMed


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.

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    • "Skeletal muscle is the major organ for fatty acid consumption, barely for lipid synthesis or storage. The increase of the lipid content in skeletal muscle which mainly results from increased fatty acid uptake and decreased β-oxidation can directly affect glucose and lipid metabolism and insulin sensitivity [39]. Several studies have indicated that inflammation may regulate fatty acid oxidation in skeletal muscles. "
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    ABSTRACT: Pattern of fat distribution is a major determinant for metabolic homeostasis. As a depot of energy, the storage of triglycerides in adipose tissue contributes to the normal fat distribution. Decreased capacity of fat storage in adipose tissue may result in ectopic fat deposition in nonadipose tissues such as liver, pancreas, and kidney. As a critical biomarker of metabolic complications, chronic low-grade inflammation may have the ability to affect the process of lipid accumulation and further lead to the disorder of fat distribution. In this review, we have collected the evidence linking inflammation with ectopic fat deposition to get a better understanding of the underlying mechanism, which may provide us with novel therapeutic strategies for metabolic disorders.
    Mediators of Inflammation 07/2014; 2014(10):418185. DOI:10.1155/2014/418185 · 3.24 Impact Factor
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    • "In contrast, endurance exercise training is characterized by IMTG accumulation and insulin sensitivity (the athlete’s paradox) (2). This variable association between IMTG accumulation and insulin responsiveness has largely been attributed to differences in the balance between lipid delivery and muscle oxidative capacity (8–10). Not surprisingly then, most studies have focused on the impact of muscle FA uptake and/or oxidation on glucose homeostasis and insulin action (11). "
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    ABSTRACT: Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity ("lipotoxicity"), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity ("the athlete's paradox"). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated animal models with decreased (skeletal muscle-specific ATGL knockout or SMAKO mice) and increased (Ckm-ATGL transgenic mice) ATGL action exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diet, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications obesity.
    Diabetes 07/2013; DOI:10.2337/db13-0500 · 8.10 Impact Factor
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    • "We found that our baseline intramyocellular lipid measurements compared to post caloric excess decreased, but intrahepatic lipid increased. These early reciprocal changes in the muscle and the liver of otherwise healthy subjects may be reflective of an adaptive increase in the oxidative capacity of the muscles (thus deceasing intramyocellular lipid) and the onset of hepatic insulin resistance [35,36]. There was also a significant increase in alanine transaminase concentration [+12.8(3.1) "
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    Cardiovascular Diabetology 01/2013; 12(1):23. DOI:10.1186/1475-2840-12-23 · 4.02 Impact Factor
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