ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2006) 12 S32

Adipose tissue and fatty acids as precursors to insulin resistance

KN Frayn

University of Oxford, Oxford, United Kingdom.

There is a long-standing belief that over-supply of fatty acids from adipose tissue might underlie insulin resistance and other components of the metabolic syndrome. Elevated NEFA concentrations may cause insulin resistance of glucose metabolism in liver and muscle, increased hepatic VLDL-triacylglycerol production, impaired endothelial function and, perhaps in the longer term, impairment of insulin secretion. Plasma non-esterified fatty acid (NEFA, or free fatty acid) concentrations tend to be higher in people with insulin resistance. There is also a belief prevalent in the literature that this results from insulin resistance of the suppression of adipose tissue lipolysis. However, when the evidence is examined critically, things are not so clear. Our own data suggest that elevated NEFA concentrations usually reflect increased fat mass. When we examine the intrinsic behaviour of adipose tissue in vivo, it seems to be relatively normal even in people with type 2 diabetes. A key issue, however, may be the degree of ‘metabolic flexibility’ of adipose tissue metabolism. This is clearly compromised in insulin resistant states. Again, however, this may not be an intrinsic defect of adipose tissue so much as a result of the elevated insulin concentrations usually seen in insulin resistance. Along with impairment of ‘metabolic flexibility’ there are alterations in the responsiveness of adipose tissue blood flow, perhaps reflecting alterations in endothelial function. These may also represent adjustments for increased adipose tissue mass. Thus, at least as far as its metabolism is concerned, adipose tissue might be more sinned against than sinning in its relationship to insulin resistance. The real culprit, in this view, is positive energy balance leading to expansion of adipose tissue mass.

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