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Metabolic flexibility

Published online by Cambridge University Press:  05 March 2007

Len Storlien ,
Nick D. Oakes  and
David E. Kelley
Len Storlien*
Affiliation:
AstraZeneca R&D, Pepparedsleden 3, Mölndal 431 83, Sweden
Nick D. Oakes
Affiliation:
AstraZeneca R&D, Pepparedsleden 3, Mölndal 431 83, Sweden
David E. Kelley
Affiliation:
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh, Pittsburgh 15213, USA
*
*Corresponding author: Professor Len Storlien Fax: +46 31 776 3704, Email: leonard.storlien@astrazeneca.com
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Abstract

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Human physiology needs to be well adapted to cope with major discontinuities in both the supply of and demand for energy. This adaptability requires ‘a clear capacity to utilize lipid and carbohydrate fuels and to transition between them’ ( Kelley et al. 2002b). Such capacities characterize the healthy state and can be termed ‘metabolic flexibility’. However, increasing evidence points to metabolic inflexibility as a key dysfunction of the cluster of disease states encompassed by the term ‘metabolic syndrome’. In obese and diabetic individuals this inflexibility is manifest in a range of metabolic pathways and tissues including: (1) failure of cephalic-phase insulin secretion (impaired early-phase prandial insulin secretion concomitant with failure to suppress hepatic glucose production and NEFA efflux from adipose tissue); (2) failure of skeletal muscle to appropriately move between use of lipid in the fasting state and use of carbohydrate in the insulin-stimulated prandial state; (3) impaired transition from fatty acid efflux to storage in response to a meal. Finally, it is increasingly clear that reduced capacity for fuel usage in, for example, skeletal muscle, as indicated by reduced mitochondrial size and density, is characteristic of the metabolic syndrome state and a fundamental component of metabolic inflexibility. Key questions that remain are how metabolic flexibility is lost in obese and diabetic individuals and by what means it may be regained.

Keywords

Metabolic flexibilityMetabolic syndromeLipid and carbohydrate utilization
Type
Symposium 6: Adipose tissue–liver–muscle interactions leading to insulin resistance
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 2 , May 2004 , pp. 363 - 368
Copyright
Copyright © The Nutrition Society 2004

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