Research studies have indicated that the comorbidity burden of mood disorders and obesity is reasonably high. Insulin signaling has been shown to modulate multiple physiological functions in the brain, indicating its association with neuropsychiatric diseases, including mood disorders. Leptin is a hormone responsible for regulating body weight and insulin homeostasis. Previous studies on db/db mice (a mouse model that carries a spontaneous genetic mutation in leptin receptor Lepr^db) have shown that they exhibit inflammation as well as neurobehavioral traits associated with mood. Therefore, targeting inflammatory pathways such as TNF-α may be an effective strategy in the treatment of obesity-linked mood disorders. The objective of this study was to investigate the effect of long-term administration of etanercept (a TNF-α blocker) on anxiety and depressive-like behaviors in db/db mice. This was performed using light/dark box, forced swim, and open field tests with lean littermate wild type (WT) mice serving as a control group. Using flow cytometry in peripheral blood, we further examined the molecular effects of etanercept on NF-κB p65, TNF-α, IL-17A, and TLR-4 expressing CD4+, CD8+, and CD14+ cells in the peripheral blood. Our data show that peripheral administration of etanercept decreased these cells in db/db mice. Furthermore, our results indicated that peripheral administration of etanercept reduced anxiety and depressive-like behaviors. Therefore, targeting TNF-α signaling might be an effective strategy for modulating obesity-associated depression and anxiety.

研究表明，情绪障碍和肥胖症的合并症负担相当高。胰岛素信号已被证明可调节大脑的多种生理功能，表明其与神经精神疾病（包括情绪障碍）有关。瘦素是负责调节体重和胰岛素稳态的激素。先前对db / db小鼠的研究（具有瘦素受体Lepr ^db的自发性基因突变的小鼠模型）表明它们表现出炎症以及与情绪有关的神经行为特征。因此，靶向炎性途径如TNF-α可能是治疗肥胖相关性情绪障碍的有效策略。这项研究的目的是研究长期服用依那西普（一种TNF-α阻滞剂）对db / db中焦虑和抑郁样行为的影响老鼠。使用明/暗盒，强制游泳和在以对照组为瘦同窝野生型（WT）小鼠的旷场试验中进行。使用外周血中的流式细胞仪，我们进一步检查了依那西普对外周血中表达CD4 +，CD8 +和CD14 +细胞的NF-κBp65，TNF-α，IL-17A和TLR-4的分子影响。我们的数据表明，依那西普的外周给药减少了db / db小鼠中的这些细胞。此外，我们的结果表明，依那西普的外围给药减少了焦虑和抑郁样行为。因此，靶向TNF-α信号可能是调节肥胖相关的抑郁和焦虑的有效策略。