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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    • "After moderate exercise training, the latter could improve their IMCL content by 21%[68]. The lipid droplets are usually aggregated in the vicinity of mitochondria and are regarded as energy source during prolonged exercise[13]. It is also well known that human skeletal muscle responds to endurance training by the formation of new capillaries[69,64,61]. "
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    ABSTRACT: PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.
    Full-text · Article · Apr 2015 · PLoS ONE
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    • "A methionine-choline-deficient high-fat diet (MCD) induced histological changes similar to those of human NASH in a murine model [12]. IMCL of soleus muscle is reportedly higher than that of the other skeletal muscles [2] [13], and IMCL of type I is higher than type II fiber types [8], while soleus muscle is mainly composed of type I fibers [14]. The objective of this study was to examine the effect of exercise training on glycogen and IMCL content of soleus muscle in NASH model rats. "

    Full-text · Article · Jan 2015 · Open Journal of Endocrine and Metabolic Diseases
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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.
    Full-text · Article · Jul 2014 · Mediators of Inflammation
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