Minireview: Inflammation and obesity pathogenesis: the hypothalamus heats up

Abstract

Obesity induced by high-fat (HF) feeding is associated with low-grade inflammation in peripheral tissues that predisposes to insulin resistance. Recent evidence suggests the occurrence of a similar process in the hypothalamus, which favors weight gain through impairment of leptin and insulin signaling. In addition to its implications for obesity pathogenesis, this hypothesis suggests that centrally targeted antiinflammatory therapies may prove effective in prevention and treatment of this disorder. This article highlights molecular and cellular mechanisms by which hypothalamic inflammation predisposes to diet-induced obesity.

Figure 1

The vicious cycle of obesity and diabetes. Energy intake in excess of energy requirements leads to a state of chronic nutrient excess that causes cellular inflammation in both peripheral tissues and the hypothalamus. The resulting activation of inflammatory pathways generates insulin and leptin resistance ultimately promoting obesity and diabetes. Therapies that prevent hypothalamic inflammation may disrupt these interlinked vicious cycles with consequent improvements in energy and glucose homeostasis.