Microglial Proliferation in Obesity: When, Where, Why, and What Does It Mean?

Abstract

Obesity is frequently associated with chronic low-grade systemic inflammation, which is believed to underlie the onset of secondary complications of this disease (1,2). In 2005, studies from the laboratory of Dr. Licio Velloso in Brazil indicated that inflammatory processes in the hypothalamus are also activated in response to diet-induced obesity and that if this inflammatory signaling is blocked, systemic glucose metabolism is improved (3). This same group later demonstrated that microglia participate in diet-induced obesity–associated hypothalamic inflammation (4), with subsequent reports suggesting that hypothalamic inflammation occurs very rapidly in response to high-fat diet (HFD) intake, even prior to substantial weight gain (5). These observations have given rise to the hypothesis that hypothalamic inflammation is a critical process in the onset of obesity and the development of its secondary complications. However, some investigators question whether central inflammation is the initial trigger or only a consequence and remain skeptical as to the real importance of this process. In a study published in this issue of Diabetes , Andre et al. (6) investigated whether inhibition of microglial proliferation in the hypothalamus can improve the metabolic response to an HFD. They infused the antimitotic drug arabinofuranosyl cytidine (AraC) intracerebroventricularly to prevent proliferation of microglia. They report that AraC prevented HFD-induced proliferation of microglia specifically in the medial basal hypothalamus and blunted the hyperphagia and increased fat mass accrual normally observed in …