Obesity, insulin resistance, Type 2 diabetes and free fatty acids

Abstract

High levels of free fatty acids have emerged as a major link between obesity and insulin resistance/Type 2 diabetes. In pancreatic β cells, free fatty acids potentiate glucose-stimulated insulin secretion precisely to the extent needed to compensate for the free fatty acid-induced insulin resistance. It is postulated that this prevents the development of Type 2 diabetes mellitus in the majority of obese, insulin-resistant individuals who have free fatty acid-mediated insulin resistance. In individuals with inherited defects of β-cell function (prediabetics), this compensation fails and hyperglycemia develops. Elevated levels of free fatty acids also activate the proinflammatory and proatherogenic nuclear factor κB pathway. Thus, elevated plasma levels of free fatty acid in obese people can produce a low-grade inflammatory state, which may contribute to accelerated atherosclerosis (coronary artery disease, strokes and peripheral arterial disease) and to nonalcoholic steatohepatitis; these conditions are increased in obesity.

Keywords::

• atherosclerotic vascular disease
• diacylglycerol
• free fatty acids
• IκB kinase
• insulin receptor substrate 1/2
• phosphoinositol 3 kinase
• protein kinase C
• Type 2 diabetes mellitus