The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders

Abstract

Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood.

Keywords: cognitive disorders; dementia; depression; diet; hypothalamic inflammation; mood disorders; obesity.

Figure 1

Daskalakis, N.P.; McGill, M.A.; Lehrner, A.; Yehuda, R. (2015). Endocrine Aspects of PTSD: Hypothalamic-Pituitary-Adrenal (HPA) Axis and Beyond. Comprehensive Guide to Post-Traumatic Stress Disorder, 1–14. doi:10.1007/978-3-319-08613-2_130-1 [133] HPA axis dysfunction in patients with major depression. Disrupted HPA axis negative feedback, leads to high cortisol levels in depressed patients.

Figure 2

A.A. Miller, S.J. Spencer / Brain, Behavior, and Immunity 42 (2014) 10–21 [58]. Proposed mechanisms of cognitive impairment in obesity. Obesity is characterized by increased proinflammatory cytokines and free fatty acids that can access central nervous system through increased BBB permeability or through ARC that lacks an effective BBB. Hypothalamic inflammation can probably affect the hypothalamic outputs to the other brain regions and the Hypothalamic-Pituitary-Adrenal (HPA) axis activity. ARC: Arcuate nucleus, BBB: Blood-brain barrier, LH: Lateral hypothalamus, PVN: Paraventricular nucleus.