Developmental thyroid hormone action on pro-opiomelanocortin-expressing cells programs hypothalamic BMPR1A depletion and brown fat activation  

作　　者：Zhaofei Wu M.Elena Martinez Victoria DeMambro Marie Francois Arturo Hernandez 

机构地区：[1]MaineHealth Institute for Research,Center for Molecular Medicine,MaineHealth,Scarborough,ME 04074,USA [2]Graduate School of Biomedical Science and Engineering,University of Maine,Orono,ME 04469,USA [3]Naomi Berrie Diabetes Center,Division of Molecular Genetics,Columbia University Irving Medical Center,New York,NY10032,USA [4]Department of Medicine,Tufts University School of Medicine,Boston,MA 02111,USA

出　　处：《Journal of Molecular Cell Biology》2022年第9期54-67,共14页分子细胞生物学报（英文版）

基　　金：We are grateful for the technical support of the Molecular Phenotyping,Histopathology and Histomorphometry,Confocal Microscopy,and Physiology Core facilities at MaineHealth Institute for Research.These core facilities are supported by grants P30GM106391,U54GM115516,and P20GM121301 from the National Institute of General Medical Sciences;This work was supported by grant DK095908(to A.H.)from the National Institute of Diabetes,Digestive and Kidney Diseases,National Institutes of Health,USA.

摘　　要：Thyroid hormone excess secondary to global type 3 deiodinase(DIO3)deficiency leads to increased locomotor activity and reduced adiposity,but also to concurrent alterations in parameters of the leptin-melanocortin system that would predict obesity.To distinguish the underlying contributions to the energy balance phenotype of Dlo3 deficiency,we generated mice with thyroid hormone excess targeted to pro-opiomelanocortin(POMC)-expressing cells via cell-specific DIO3 inactivation.These mice exhibit a male-specific phenotype of reduced hypothalamic Pomc expression,hyperphagia,and increased activity in brown adipose tissue,with adiposity and serum levels of leptin and thyroid hormones remained normal.These male mice also manifest a marked and widespread hypothalamic reduction in the expression of bone morphogenetic receptor 1a(BMPR1A),which has been shown to cause similar phenotypes when inactivated in PoMC-expressing cells.Our results indicate that developmental overexposure to thyroid hormone in PoMC-expressing cells programs energy balance mechanisms in a sexually dimorphic manner by suppressing adult hypothalamic BMPR1A expression.

关 键 词：thyroid hormone type 3 deiodinase(DIO3) bone morphogenetic receptor 1a(BMPR1A) pro-opiomelanocortin(POMC) HYPERPHAGIA brown adipose tissue CORTICOSTERONE 

分 类 号：R581.1[医药卫生—内分泌]