Obesity- and High-Fat-Diet-Induced Neuroinflammation: Implications for Autonomic Nervous System Dysfunction and...

Obesity is a multifactorial condition linked to severe health complications, including cardiovascular diseases and endothelial dysfunction. Both obesity and high-fat diets (HFDs) are strongly associated with neuroinflammation, particularly in the hypothalamus. The autonomic nervous system (ANS), which controls involuntary physiological processes, is critical for maintaining cardiovascular health, and its dysfunction is implicated in endothelial disorders. With its homeostatic control centers located in the hypothalamus and brainstem, a crucial question arises: could obesity- and HFD-induced neuroinflammation disrupt central ANS structures, leading to ANS dysfunction and subsequent endothelial disorders? This review examined whether neuroinflammation caused by obesity and HFD contributes to endothelial dysfunction through the dysregulation of the ANS. Our analysis revealed that hypothalamic inflammation linked to obesity and an HFD is associated with sympathetic hyperactivity and endothelial disorders. Identified molecular mechanisms include the influence of inflammatory cytokines, activation of the NF-κB/IKK-β pathway, microglial activation mediated by angiotensin II, circulating mitochondria triggering cGAS activation, and the stimulation of the TLR4 pathway. Our findings suggest that hypothalamic inflammation may play a central role in the interplay between obesity/an HFD, ANS dysfunction, and endothelial disorders.