Loss of the centrosomal protein Cenpj leads to dysfunction of the hypothalamus and obesity in mice  

作　　者：Wenyu Ding Changjiang Zhang Baisong Wang Xin Zhou Le Sun Suijuan Zhong Jing Liu Junjing Zhang Xiaoqun Wang Qian Wu 

机构地区：[1]State Key Laboratory of Cognitive Neuroscience and Learning,Beijing Normal University,Beijing 100875,China [2]IDG/McGovern Institute for Brain Research,Beijing Normal University,Beijing 100875,China [3]State Key Laboratory of Brain and Cognitive Science,CAS Center for Excellence in Brain Science and Intelligence Technology,Institute of Brain-Intelligence Technology(Shanghai),Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [4]University of Chinese Academy of Sciences,Beijing 100049,China [5]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China [6]Advanced Innovation Center for Human Brain Protection,Beijing Institute for Brain Disorders,Capital Medical University,Beijing 100069,China

出　　处：《Science China(Life Sciences)》2021年第3期419-433,共15页中国科学（生命科学英文版）

基　　金：the National Basic Research Program of China(2017YFA0102601,2019YFA0110101,2017YFA0103303);the National Natural Science Foundation of China(31671072,91732301,31771140,81891001);Strategic Priority Research Program of the Chinese Academy of Sciences,the Grants of Beijing Brain Initiative of Beijing Municipal Science and Technology Commission(Z181100001518004);Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning.

摘　　要：Cenpj is a centrosomal protein located at the centrosomes and the base of cilia,it plays essential roles in regulating neurogenesis and cerebral cortex development.Although centrosomal and cilium dysfunction are one of the causes of obesity,insulin resistance,and type 2 diabetes,the role that Cenpj plays in the regulation of body weight remains unclear.Here,we deleted Cenpj by crossing Cenpjflox/flox mice with Nkx2.1-Cre mice.Loss of the centrosomal protein Cenpj in Nkx2.1-expressing cells causes morbid obesity in mice at approximately 4 months of age with expended brain ventricles but no change of brain size.We found that hypothalamic cells exhibited reduced proliferation and increased apoptosis upon Cenpj depletion at the embryonic stages,resulting in a dramatic decrease in the number of Proopiomelanocortin(POMC)neurons and electrophysiological dysfunction of NPY neurons in the arcuate nucleus(ARC)in adults.Furthermore,depletion of Cenpj also reduced the neuronal projection from the ARC to the paraventricular nucleus(PVN),with decreased melanocortin-4 receptors(MC4R)expression in PVN neurons.The study defines the roles that Cenpj plays in regulating hypothalamus development and body weight,providing a foundation for further understanding of the pathological mechanisms of related diseases.

关 键 词：arcuate nucleus centrosomal protein Cenpj Nkx2.1 HYPOTHALAMUS paraventricular nucleus 

分 类 号：R338[医药卫生—人体生理学]