Neurobehavioral Consequences of Obesity: The Role of Inflammation

Abstract

Objective Obesity is a global health concern linked to neuroinflammation, cognitive decline, and depression. Tumor necrosis factor-α (TNF-α) is a key mediator of these effects, and its inhibition may offer therapeutic benefits. This study investigated whether etanercept (ETN), a TNF-α inhibitor, prevents neurobehavioral alterations induced by a cafeteria (CAF) diet in rats. Methods Male rats were assigned to control, CAF, or CAF + ETN groups for 12 weeks. Cognitive and affective behaviors were assessed by the Morris water maze, passive avoidance, forced swimming, and sucrose preference tests. Hippocampal TNF-α, interleukin-1β, and brain-derived neurotrophic factor (BDNF) levels were measured. Results CAF-fed rats developed obesity, memory impairment, and depression-like behaviors, accompanied by increased proinflammatory cytokines and reduced BDNF immunoreactivity. ETN attenuated weight gain and improved cognitive and emotional performance with normalized hippocampal proinflammatory cytokines levels. After ETN treatment, BDNF levels significantly increased compared to the CAF group but still remained lower than the controls. Conclusion The results of the study indicate that TNF-α inhibition alleviates obesity-induced neuroinflammation and rescues cognitive and emotional behavioral impairments, while only partially restoring hippocampal BDNF levels. These results suggest a potential link between TNF-α inhibition and the mitigation of obesity-associated neurobehavioral dysfunction through the suppression of hippocampal neuroinflammation.