Inhibition Of Adipose Tissue Lipolysis Increases Intramuscular Lipid Use In Type 2 Diabetes Patients

Loon, L.J. van; Manders, Ralph J.; Koopman, René; Kaastra, Brechje; Stegen, Jos H. C. H.; Gijsen, Annemie P.; Keizer, H. A.

doi:10.1249/00005768-200505001-01414

Cited by 1 publication

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“…Consequently, a combined exercise and pharmacological intervention that elevates both intramuscular lipid and/or glycogen use could likely be more effective to increase skeletal muscle insulin sensitivity. In accordance, lipolytic inhibition in combination with a single bout of moderate intensity exercise in overweight, type 2 diabetes patients resulted in a greater increase in insulin sensitivity during post-exercise recovery when compared to exercise only [99]. More research is warranted to establish the more long-term effects of combining exercise with lipolytic inhibition as a means to augment the benefits of exercise intervention to prevent and/or treat skeletal muscle insulin resistance.…”

Section: Current Ideas Speculations and Future Researchmentioning

confidence: 92%

“…Elevated plasma FFA levels have recently been shown to inhibit the mobilisation and/or oxidation rate of the IMTG stores [99,100]. In accordance, by reducing circulating plasma FFA levels through pharmacological inhibition of adipose tissue lipolysis, IMTG utilisation can be improved significantly both at rest and during exercise in overweight type 2 diabetes patients [99]. This offers an attractive explanation for the origin of the elevated IMTG stores in the sedentary, obese and/or type 2 diabetes patients (Fig.…”

Section: Intramyocellular Lipid As a Substrate Source During Exercisementioning

confidence: 93%

“…This could be attributed to the elevated plasma FFA levels that are associated with the obese and/or type 2 diabetic states. Elevated plasma FFA levels have recently been shown to inhibit the mobilisation and/or oxidation rate of the IMTG stores [99,100]. In accordance, by reducing circulating plasma FFA levels through pharmacological inhibition of adipose tissue lipolysis, IMTG utilisation can be improved significantly both at rest and during exercise in overweight type 2 diabetes patients [99].…”

Section: Intramyocellular Lipid As a Substrate Source During Exercisementioning

confidence: 99%

“…3). In this population, the excess IMTG accretion is attributed to the elevated plasma FFA availability and FA uptake [45,65,75,85], the subsequent FFA-induced inhibition of IMTG utilisation [99,100] and/or a reduced capacity to oxidize FA [4,5,41]. The structural imbalance between FFA uptake, TG storage and FA oxidation leads to a progressive intramyocellular accumulation of both TG and FA metabolites (such as fatty acyl-CoA, ceramides and diacylglycerol), of which the latter have been shown to induce defects in the insulin signalling cascade [1,6,16,18,36,45,77,85,105].…”

Section: Intramyocellular Lipid As a Substrate Source During Exercisementioning

confidence: 99%

“…Recent studies by van Loon et al in endurancetrained athletes [100] and type 2 diabetes patients [99] show that IMTG and muscle glycogen use can be increased by combining exercise with pharmacological inhibition of adipose tissue lipolysis. These findings could be of clinical relevance to the prevention and/or treatment of skeletal muscle insulin resistance.…”

Section: Current Ideas Speculations and Future Researchmentioning

confidence: 99%

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

Loon

Goodpaster

2005

Pflugers Arch - Eur J Physiol

180

144

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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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Section: Current Ideas Speculations and Future Researchmentioning

confidence: 92%

Section: Intramyocellular Lipid As a Substrate Source During Exercisementioning

confidence: 93%

Section: Intramyocellular Lipid As a Substrate Source During Exercisementioning

confidence: 99%

Section: Intramyocellular Lipid As a Substrate Source During Exercisementioning

confidence: 99%

Section: Current Ideas Speculations and Future Researchmentioning

confidence: 99%

See 3 more Smart Citations

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

Loon

Goodpaster

2005

Pflugers Arch - Eur J Physiol

180

144

View full text Add to dashboard Cite

show abstract

Inhibition Of Adipose Tissue Lipolysis Increases Intramuscular Lipid Use In Type 2 Diabetes Patients

Cited by 1 publication

References 0 publications

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

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

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