Hypothalamic inflammation and malfunctioning glia in the pathophysiology of obesity and diabetes: Translational significance

Preclinical studies have suggested that chronic inflammation in the brain might be associated with multiple metabolic disorders, including obesity and diabetes. In particular, hypothalamic inflammation interferes with the endocrine system and modulates nutritional homeostasis, leading to metabolic alterations and consequent pathologies. With regard to the mechanisms underlying molecular and cellular pathogenesis, neurons, non-neuronal cells, and the crosstalk between them have gained particular attention. Specifically, malfunctioning glia have recently been implicated as an important component of pathological hypothalamic inflammation. Hypothalamic inflammation modulates food intake, energy expenditure, insulin secretion, hepatic glucose production, and glucose and fatty acid metabolism. Moreover, growing evidence suggests that hypothalamic inflammation is intrinsically associated with the pathogenesis of obesity, diabetes, and their dysfunctional consequences. However, the translational significance of hypothalamic inflammation has not yet been fully explored. In this review, we cover recent advances suggesting that hypothalamic inflammation and glia play a central role in the ontology of obesity, diabetes, and their complications. Finally, we explore the possibilities and challenges of targeting hypothalamic inflammation as a potential therapeutic strategy.