Mild Suppression of Hyperinsulinemia to Treat Obesity and Insulin Resistance

Insulin plays roles in lipid uptake, lipolysis, and lipogenesis, in addition to controlling blood glucose levels. Excessive circulating insulin is associated with adipose tissue expansion and obesity, yet a causal role for hyperinsulinemia in the development of mammalian obesity has proven controversial, with many researchers suggesting it as a consequence of insulin resistance. Recently, evidence that specifically reducing hyperinsulinemia can prevent and reverse obesity in animal models has been presented. Our experiments, and others in this field, question the current dogma that hyperinsulinemia is a response to obesity and/or insulin resistance. In this review, we discuss preclinical evidence in the context of the broader literature and speculate on the possibility of clinical translation of alternative approaches for treating obesity.