抑郁症与糖尿病共病的运动干预机制——瘦素抵抗假说

Mechanism of Exercise Intervention against Comorbid Depression and Diabetes——Hypothesis of Leptin Resistance

糖尿病患者罹患抑郁症现象正吸引越来越多的关注,常用抗抑郁药又会增加糖尿病风险。运动可促进抑郁患者和糖尿病人的康复,但机制却不明确,更未见运动对二者共病机理研究。文献表明,对患抑郁症的肥胖人群而言,治疗应聚焦瘦素下游和瘦素抵抗通路。JAK2/STAT 3是介导瘦素信号主要通路,其中的调解因子都需接受瘦素受体LepRb磷酸化的始动调节,而炎性细胞因子ICK则贯穿IKKβ/NFκB通路,二者都受SOCS3的抑制。由此提出,经由LepRb/ICK-SOCS3通路的瘦素抵抗可能介导了抑郁症与糖尿病共病的运动干预机制。这将有助于阐明抑郁症与糖尿病的共病机制,也可为二者的共病诊治提供新的药物靶点和非药物干预手段。

Diabetic patients with depression phenomenon is attracting more and more attention,long-term use of tricyclic antidepressants and SSRIs will increase the risk of diabetes.Exercise promotes recovery of depressive patients and patients with diabetes,but the mechanisms underlying the exercise intervention still remain unknown.For diabetes patients with co-morbid depression,focus should be on downstream of leptin signaling and leptin resistance.JAK2/STAT3 pathway is involved in leptin signaling via leptin receptor（LepRb）phosphorylation,and inflammatory cytokines（ICK）induces IKKβ/NFκB activation.JAK2/STAT3 and IKKβ/NFκB pathway are inhibited by the suppressor of cytokine signaling 3（SOCS3）in leptin resistance.Therefore,the current study puts forward that LepRb/ICK-SOCS3 pathway mediates leptin resistance in exercise intervention for comorbidity of depression and diabetes.The prospective findings may contribute to our understanding of the comorbidity between depression and diabetes,and suggest a new target or guide for pharmacological research and development against metabolic diseases.