Beyond Dietary Fatty Acids as Energy Source: A Point of View for the Prevention and Management of Type 2 Diabetes

Abstract

Dietary fatty acids have been traditionally viewed as substrates for the generation of highenergy molecules and as precursors for the biosynthesis of macromolecules. However, accumulating data from multiple lines of evidence suggest that dietary fatty acids are linked to the pathogenesis of type 2 diabetes, which involves abnormalities in both insulin secretion and action (Lopez et al., 2010). Dietary fatty acids are absorbed into epithelial cells of the small intestine, are assembled into nascent triglyceride-rich lipoproteins, enter the bloodstream, and are transported to peripheral tissues. Therefore, the main physiological — but sometimes pathological — contribution to plasma triglycerides and tissue fatty acids, in terms of both quantity and quality, occurs during the postprandial period (Miles & Nelson, 2007). Acute elevation in plasma triglycerides, which may produce local elevation of fatty acids in beta-cells, is related to the increase of glucose-induced insulin secretion (Lopez et al., 2008; Lopez et al., 2010). Adipose tissue serves as a triglyceride storage site and, when necessary, stored triglycerides in adipocytes can be hydrolyzed by their adipose triglyceride and hormone-sensitive lipases to release fatty acids into the bloodstream. Excessive rates of lipid turnover have been shown to precede the development of type 2 diabetes in subjects with a family history of type 2 diabetes and nondiabetic obese individuals (Cusi, 2009). Decreased insulin sensitivity in adipose tissue is characterized by the increase of lipolysis and plasma fatty acid levels despite hyperinsulinemia, and impaired suppression of plasma fatty acid levels by insulin. This elevation in the plasma fatty acids, if chronic, induces a decrease in hepatic and skeletal muscle insulin sensitivity and detrimental effects on beta-cell function, which has been referred to as lipotoxicity (Giacca et al., 2011). Here, we review studies in insulin-secreting cell lines, islet cells, animal models, and human beings that have informed our current understanding of the mechanistic links among dietary fatty acids, beta-cell function, and insulin sensitivity.