实验室在《Molecular Psychiatry》发表题为“Role of the adipose PPARγ-adiponectin axis in susceptibility to stress and depression/anxiety-related behaviors”的文章.
课题组于12月13日在《Molecular Psychiatry》 （精神病学1区期刊，IF：13.3）上在线发表研究论文 “Role of the adipose PPARγ-adiponectin axis in susceptibility to stress and depression/anxiety-related behaviors”。
抑郁和焦虑是目前社会中最常见的心理疾病，严重影响人们的生活和工作，近年来患病率病逐年渐增加，给社会和经济带来沉重负担。本课题组在国际上首先提出精神疾病的“代谢假说”，发现了内分泌系统中的脂肪组织与情绪调节相关的神经系统之间的相互作用。本研究在 “代谢假说”基础上，进一步探讨了脂肪组织在应激诱导的抑郁行为中的作用。应用慢性社会挫败（chronic social defeat）应激模型发现小鼠对应激诱导的社会逃避抑郁行为的易感性与脂肪中脂联素上游调控基因PPARγ2水平之间存在显著相关性。利用PPARγ激动剂rosiglitazone激活PPARγ信号通路具有抗抑郁和抗焦虑作用，并伴有脂肪和血液中脂联素水平的升高。Rosiglitazone的作用可以被脂联素的缺失或PPARγ拮抗剂GW9662所阻断。本研究在国际上首次证明脂肪组织PPARγ-脂联素信号系统在应激易感性中的作用和对抑郁、焦虑行为的调控，并为开发新型抗抑郁和焦虑药物提供了新的靶点。
Mol Psychiatry. 2016 Dec 13. doi: 10.1038/mp.2016.225. [Epub ahead of print]
Role of the adipose PPARγ-adiponectin axis in susceptibility to stress and depression/anxiety-related behaviors.
Guo M1, Li C1, Lei Y2, Xu S1, Zhao D1, Lu XY1,2,3.
1Institute for Metabolic and Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, China.
2Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
3Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Adaptive responses to stressful stimuli involving behavioral, emotional and metabolic changes are orchestrated by the nervous and endocrine systems. Adipose tissue has been recognized as a highly active metabolic and endocrine organ, secreting adipokines that operate as hormones to mediate the crosstalk with other organs including the brain. The role of adipose tissue in sensing and responding to emotional stress and in behavioral regulation, however, remains largely unknown. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcriptional factor controlling adipokine gene expression. Here we show that chronic social defeat stress decreases messenger RNA and protein levels of PPARγ in adipose tissue of susceptible but not resilient mice, which was correlated with social avoidance behavior. A corresponding reduction in adipose adiponectin production was observed in susceptible mice. Rosiglitazone, a blood-brain barrier-impermeant PPARγ-selective agonist, elicited antidepressant- and anxiolytic-like behavioral effects in wild-type mice, with a concurrent increase in plasma adiponectin levels. These effects of rosiglitazone were absent in mice lacking adiponectin but having normal PPARγ expression in adipose tissue and brain. Moreover, pretreatment with the PPARγ-selective antagonist GW9662 blocked rosiglitazone-induced adiponectin expression and antidepressant/anxiolytic-like effects. Together, these results suggest that the behavioral responses to rosiglitazone are mediated through PPARγ-dependent induction of adiponectin. Our findings support an important role for the adipose PPARγ-adiponectin axis in susceptibility to stress and negative emotion-related behaviors. Selectively targeting PPARγ in adipose tissue may offer novel strategies for combating depression and anxiety.Molecular Psychiatry advance online publication, 13 December 2016; doi:10.1038/mp.2016.225