Neuroinflammatory basis of metabolic syndrome

Abstract

Inflammatory reaction is a fundamental defense mechanism against threat towards normal integrity and physiology. On the other hand, chronic diseases such as obesity, type 2 diabetes, hypertension and atherosclerosis, have been causally linked to chronic, low-grade inflammation in various metabolic tissues. Recent cross-disciplinary research has led to identification of hypothalamic inflammatory changes that are triggered by overnutrition, orchestrated by hypothalamic immune system, and sustained through metabolic syndrome-associated pathophysiology. While continuing research is actively trying to underpin the identity and mechanisms of these inflammatory stimuli and actions involved in metabolic syndrome disorders and related diseases, proinflammatory IκB kinase-β (IKKβ), the downstream nuclear transcription factor NF-κB and some related molecules in the hypothalamus were discovered to be pathogenically significant. This article is to summarize recent progresses in the field of neuroendocrine research addressing the central integrative role of neuroinflammation in metabolic syndrome components ranging from obesity, glucose intolerance to cardiovascular dysfunctions.

Keywords: CNS; Hypothalamus; IKKβ/NF-κB pathway; Inflammation; Obesity; Type 2 diabetes.

Fig. 1

Role of hypothalamic neuroinflammation in metabolic disorders. Overnutrition activates pro-inflammatory IKK-β/NF-κB in the hypothalamic neurons, which occurs through intracellular neuronal stressors like ER stress, defective autophagy machinery as well as glia-neuron inflammatory cross-talk, collectively leading to hypothalamic metabolic deregulations that cause a spectrum of metabolic disorders.