Figure 2. Role of neuroinflammation in overnutrition-induced diseases.

Under conditions of chronic overnutrition, the mediobasal hypothalamus (MBH) is affected by chronic overnutrition, a prolonged and persistent nutritional changes in the body which primarily arises from environmental and social-behavioral factors such as Western diet, sedentary lifestyle and disrupted diurnal order of life. These lead to IKKβ/NF-κB-directed inflammatory response and several intracellular organelle stresses in the MBH. Many of these cellular and molecular components promote each other, resulting in overnutrition-related neuroinflammation. Such neuroinflammation impairs intracellular hormonal signaling of regulatory neurons and disrupts neurogenesis through depletion of NSCs. The progression of overnutrition-related diseases such as obesity and diabetes, characterized by hyperlipidemia and hyperglycemia, secondarily leads to pathophysiological overnutrition in the body’s internal environment and exacerbates this mechanism. In summary, neuroinflammation employs multiple pathways including hormonal signaling dysfunction and neurodegeration to link overnutrition to overnutrition-related diseases such as obesity, diabetes and related complications. Abbreviations: TLRs: toll-like receptors; NSCs: neural stem cells.