The etiology of obesity-induced insulin resistance

Insulin is an essential hormone with important roles in glucose homeostasis and anabolicmetabolism. Cellular and/or molecular defects in insulin action result in a state of insulinresistance, which is an essential feature of the diseases type 2 diabetes and the metabolicsyndrome. One of the largest correlations to insulin resistance is obesity; specifically theenlargement of adipose tissue in the abdomen. This correlation is unmistakably obvious todayas the twin epidemics of obesity and type 2 diabetes have co-emerged. One of the biggestchallenges in the field of diabetes research is to determine how the increase in visceraladiposity leads to impaired insulin action. Recently, two hypothetical mechanisms havetranspired: (a) obesity shifts the secretory profile of adipose tissue to favor a reduction innutrient uptake by creating insulin resistance, and/or (b) overloaded fat cells and increasedcaloric intake common in obesity leads to inappropriate storage of lipids in non-adiposetissues where they antagonize insulin action. This review summarizes findings implicatingeach mechanism, alone or in concert, in the etiology of obesity-induced insulin resistance.