Effect of saturated and insaturated free fatty acids on skeletal muscle insulin resistance and metabolism
Abstract
Free fatty acids (FFA) play an important physiological role in the body, however, chronically elevated plasma FFA are associated with various pathophysiological consequences. Elevated FFA concentrations are linked with the onset of peripheral insulin resistance.
Skeletal muscle is an important target tissue for the action of FFA. It was shown that the type of FFA is crucial in the determination of their effect, i.e. the length and the degree of saturation of FFA.
Detrimental effects of saturated FFA and, on the other hand, positive effects of unsaturated FFA were shown in cell culture experiments but also in animal and human studies. However, the main mechanism by which saturated fatty acids mediate their effects in skeletal muscle have not been fully elucidated.
The main candidates include an increase in production of lipid metabolites like ceramide or diacylglycerol, increased oxidative stress and activation of inflammatory pathways. These phenomena can lead to an induction of insulin resistance, mitochondrial dysfunction and cell apoptosis.
Understanding of mechanisms by which unsaturated fatty acids prevent these effects is an important step in the development of new interven tion strategies and towards a decrease of the prevalence of diseases associated with insulin resistance.