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Developmental thyroid hormone action on pro-opiomelanocortin-expressing cells programs hypothalamic BMPR1A depletion and brown fat activation
Zhaofei Wu1 , M. Elena Martinez1 , Victoria DeMambro1,2 , Marie Francois3 , Arturo Hernandez1,2,4,*
1MaineHealth Institute for Research, Center for Molecular Medicine, MaineHealth, Scarborough, ME 04074, USA
2Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME 04469, USA
3Naomi Berrie Diabetes Center, Division of Molecular Genetics, Columbia University Irving Medical Center, New York, NY 10032, USA
4Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA
*Correspondence to:Arturo Hernandez ,
J Mol Cell Biol, Volume 14, Issue 9, September 2022, mjac078,
Keyword: thyroid hormone, type 3 deiodinase (DIO3), bone morphogenetic receptor 1a (BMPR1A), pro-opiomelanocortin (POMC), hyperphagia, brown adipose tissue, corticosterone

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 DIO3 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 rem