Abnormal dietary fatty acid metabolic partitioning in insulin resistance and Type 2 diabetes

Experimental overexposure of lean tissues to fatty acids has been linked to ectopic fat deposition and the development of insulin resistance and impaired glucose-stimulated insulin secretion in animal and human studies. Ectopic fat deposition in lean tissues also spontaneously occurs early during the natural history of Type 2 diabetes. Potential mechanisms for this ectopic fat deposition include impaired lean tissue fatty acid oxidation, in situ synthesis of fatty acids (de novo lipogenesis) and/or overexposure of lean tissues to circulating fatty acids. The latter occurs from at least two different circulating pools: nonesterified fatty acids ('free' fatty acids); and triglyceride-rich lipoproteins (mostly chylomicrons and VLDL). This review will summarize current knowledge from investigation in humans about the potential contribution of these mechanisms to lean tissue fatty acid overexposure in the development of Type 2 diabetes. A special emphasis will be made on adipose tissue control of dietary fatty acid partitioning and on recent advances in noninvasive metabolic imaging of this process.