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Acta Physiol (Oxf). 2006 Jan;186(1):5-16.

The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity.

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1
Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada. ddyck@uoguelph.ca

Abstract

Several adipose-derived cytokines (adipokines) have been suggested to act as a link between accumulated fat mass and altered insulin sensitivity. Resistin and tumour necrosis factor-alpha (TNF-alpha) have been implicated in impairing insulin sensitivity in rodents; conversely, two other adipokines, leptin and adiponectin, increase insulin sensitivity in lean and obese rodents. Currently, there is considerable focus on the concept that lipid accumulation in skeletal muscle leads to the development of insulin resistance. Adiponectin and leptin have each been demonstrated to increase rates of fatty acid (FA) oxidation and decrease muscle lipid content, which may in part be the underlying mechanism to their insulin sensitizing effect. These effects on FA metabolism appear to be mediated in part through the activation of AMP-activated protein kinase. Evidence derived from animal and human studies suggests that the ability of leptin and adiponectin to stimulate FA oxidation in muscle is impaired in the obese condition. Thus, leptin and adiponectin resistance may be an initiating factor in the accumulation of intramuscular lipids, such as diacylglycerol and ceramide, and the ensuing development of insulin resistance. Lifestyle factors such as diet and exercise are able to restore the sensitivity of muscle to leptin. The actual physiological roles of resistin and TNF-alpha in altering muscle lipid metabolism are more controversial, but each has been shown to directly impair insulin signalling and consequently, insulin stimulated glucose uptake in muscle. However, the possibility that resistin and TNF-alpha reduces insulin sensitivity in muscle by directly impairing FA metabolism in this tissue leading to lipid accumulation, has been virtually unexamined. Thus, the contribution of various adipokines to the development of insulin resistance is complex and not fully understood. Finally, the effects of these adipokines on metabolism and insulin sensitivity are generally studied in isolation, making it difficult to predict the interactive effects and the net impact on insulin sensitivity.

[Indexed for MEDLINE]

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