The etiology of obesity-induced insulin resistance

Insulin is an essential hormone with important roles in glucose homeostasis and anabolic metabolism. Cellular and/or molecular defects in insulin action result in a state of insulin resistance, which is an essential feature of the diseases type 2 diabetes and the metabolic syndrome. One of the largest correlations to insulin resistance is obesity; specifically the enlargement of adipose tissue in the abdomen. This correlation is unmistakably obvious today as the twin epidemics of obesity and type 2 diabetes have co-emerged. One of the biggest challenges in the field of diabetes research is to determine how the increase in visceral adiposity leads to impaired insulin action. Recently, two hypothetical mechanisms have transpired: (a) obesity shifts the secretory profile of adipose tissue to favor a reduction in nutrient uptake by creating insulin resistance, and/or (b) overloaded fat cells and increased caloric intake common in obesity leads to inappropriate storage of lipids in non-adipose tissues where they antagonize insulin action. This review summarizes findings implicating each mechanism, alone or in concert, in the etiology of obesity-induced insulin resistance.