Pflügers Archiv

, Volume 451, Issue 5, pp 606–616 | Cite as

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

  • Luc J.C. van LoonEmail author
  • Bret H. Goodpaster
Invited Review


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.


Metabolic paradox Mitochondrial dysfunction IMTG IMCL Insulin resistance Endurance training Type 2 diabetes 



Dr. L.J.C. van Loon was supported by a grant from the Netherlands Organisation for Scientific Research (NWO). Dr. B.H. Goodpaster was supported by a grant from the National Institutes of Health (R01 AG20128-01) and the American Diabetes Association. The electron microscopy photograph was kindly provided by Prof. H. Hoppeler. Our thanks go out to all the people that assisted in any way in the described studies and especially to all the volunteers that were involved worldwide.


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© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Departments of Movement Sciences and Human Biology, Nutrition Research Institute MaastrichtMaastricht UniversityMaastrichtThe Netherlands
  2. 2.Division of Endocrinology and Metabolism, Department of Medicine, School of MedicineUniversity of PittsburghPittsburghUSA

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