Exercise and ER stress in hypothalamus.

<p>Overnutrition increases hypothalamic activation of IKKβ/NF-κB and ER stress (they enhance each other), which leads to insulin and leptin resistance in the hypothalamus, hyperphagia, and obesity. Exercise reduces hypothalamic IKKβ/NF-κB activation and ER stress through a mechanism involving IL-6 and IL-10. As a result of this effect, insulin and leptin sensitivity, and consequently food intake, are restored. Whether hypothalamic lipotoxicity contributes to increased activation of IKKβ/NF-κB and ER stress will require further investigation. 3V: third ventricle; ARC: arcuate nucleus of the hypothalamus; DMH: dorsomedial nucleus of the hypothalamus; IKKβ/NF-κB: inhibitor of nuclear factor kappa-B kinase subunit beta/nuclear transcription factor kappa-B; LHA: lateral hypothalamic area; PVH: paraventricular nucleus of the hypothalamus; VMH: ventromedial nucleus of the hypothalamus.