Fatty acid activated membrane receptor function and fat in the nutritional prevention of diabetes type 2

Abstract

The mechanisms of intracellular free fatty acid (FFA) effects on insulin secretion and signaling are known for many years, however, their effects exerted by extracellular route, via membrane receptors, have been recognized only recently. There are two main groups of membrane receptors activated by FFA: Toll like receptors (TLRs) engaged in nonspecific immunity, activated by bacterial and viral antigens and Gprotein coupled receptors (GPRs). Activation of TLR2 and 4 by saturated acids leads to activation of NFkB and induction of proinflammatory cytokines. Knockout of TLR2 or TLR4 protects from the effects of high fat diet — insulin resistance and beta-cell dysfunction. GPRs mediate insulinotropic effects of FFA exerted either directly on pancreatic beta cells (GPR- 40) or indirectly, in enteroendocrine cells, by stimulation of GLP-1 and GIP release (GPR-120). The effects of cholecystokinin, GLP-1 and GIP secretion through GPR-120 activation were shown for monounsaturated and polyunsaturated omega 3 fatty acids. In adipose tissue omega 3 fatty acids counteract the proinflammatory cytokine signaling and their synthesis. Short chain fatty acids utilize adipose GPR-43 for stimulation of leptin secretion and GPR-42 and 43 for stimulation of PYY and serotonin secretion by enteroendocrine cells. The intensive research of GPR ligands pharmacologically efficient in diabetes type 2 therapy are currently conducted. Comprehensive characterization of the effects of dietary fatty acids on GPR activation could enable the optimization of nutritional prevention and management of diabetes type 2.
(Diabet. Prakt. 2011; 12, 2: 42–51)