5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 8–11 July 2003, Le Meridien Montparnasse, Paris, France

ADIPOSE TISSUE AND INSULIN RESISTANCE

Antiviral Therapy 2003; 8:L1 (abstract P2)

K Frayn
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, UK

There are many possible links between adipose tissue, insulin resistance, dyslipidaemia and hypertension. Much attention has been paid in recent years to the potential role of adipocytokines and other factors secreted from adipocytes. Whilst the evidence for involvement of some of these is reasonably strong, there is an alternative (perhaps complementary) view that well-understood metabolic processes may be involved. It can be argued that adipose tissue plays a vital role in "buffering" the daily influx of fatty acids entering the circulation in just the same way that the liver "buffers" the daily influx of carbohydrate and prevents excessive excursions of plasma glucose concentration. If excessive glucose excursions occur, we know the condition as diabetes mellitus. If excessive fatty acid excursions occur, the result is deposition of fat in tissues other than adipose, including skeletal muscle, liver and pancreas (ectopic fat deposition). Fat deposition in these non-adipose tissues is closely associated with insulin resistance and, in the case of the pancreas, with increased risk of β cell failure. This view throws the emphasis on the normal "metabolic flexibility" of adipose tissue. The adipocyte normally has a very dynamic pattern of metabolism. In the fasting state it releases fatty acids, to be used as a substrate by other oxidative tissues. In the fed state, however, the adipocyte changes to "absorb" fatty acids from the circulation (mainly from circulating triacylglycerol). The direction of net flux of fatty acids across the adipocyte membrane is constantly changing with nutritional state. It is this capacity to absorb fatty acids from the circulation that gives adipose tissue its special role in protecting other tissues from excessive fatty acid flux. There is plenty of evidence for "metabolic inflexibility" of adipose tissue associated with insulin-resistant states such as obesity (large fat cells are inherently less active than small ones). Alternatively, in conditions with a deficiency of adipose tissue, such as lipodystrophy, there may simply not be sufficient adipose tissue to cope with incoming fat. This view, therefore, reconciles the fact that insulin resistance is associated both with an excess and a deficiency of adipose tissue.

Presenting author: K Frayn

2003-07-08
P2

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