PMID- 32166324 OWN - NLM STAT- MEDLINE DCOM- 20200731 LR - 20240425 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 161 IP - 4 DP - 2020 Apr 1 TI - Neurochemical Characterization of Brainstem Pro-Opiomelanocortin Cells. LID - 10.1210/endocr/bqaa032 [doi] LID - bqaa032 AB - Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by quantitative PCR. In situ hybridization histochemistry of endogenous Pomc mRNA and immunohistochemical analysis of eGFP revealed that POMC is primarily localized within the caudal NTS. Neurochemical analysis indicated that POMCNTS is not co-expressed with tyrosine hydroxylase (TH), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), brain-derived neurotrophic factor (BDNF), nesfatin, nitric oxide synthase 1 (nNOS), seipin, or choline acetyltransferase (ChAT) cells, whereas 100% of POMCNTS is co-expressed with transcription factor paired-like homeobox2b (Phox2b). We observed that 20% of POMCNTS cells express receptors for adipocyte hormone leptin (LepRbs) using a PomceGFP:LepRbCre:tdTOM double-reporter line. Elevations in endogenous or exogenous leptin levels increased the in vivo activity (c-FOS) of a small subset of POMCNTS cells. Using ex vivo slice electrophysiology, we observed that this effect of leptin on POMCNTS cell activity is postsynaptic. These findings reveal that a subset of POMCNTS cells are responsive to both changes in energy status and the adipocyte hormone leptin, findings of relevance to the neurobiology of obesity. CI - (c) Endocrine Society 2020. FAU - Georgescu, Teodora AU - Georgescu T AD - Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK. AD - Department of Pharmacology, University of Cambridge, Cambridge, UK. AD - Centre for Neuroendocrinology & Department of Anatomy, University of Otago, Dunedin, New Zealand. FAU - Lyons, David AU - Lyons D AD - Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK. FAU - Doslikova, Barbora AU - Doslikova B AD - Department of Pharmacology, University of Cambridge, Cambridge, UK. FAU - Garcia, Ana Paula AU - Garcia AP AD - Department of Pharmacology, University of Cambridge, Cambridge, UK. FAU - Marston, Oliver AU - Marston O AD - Department of Pharmacology, University of Cambridge, Cambridge, UK. FAU - Burke, Luke K AU - Burke LK AD - Department of Pharmacology, University of Cambridge, Cambridge, UK. FAU - Chianese, Raffaella AU - Chianese R AD - Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK. FAU - Lam, Brian Y H AU - Lam BYH AD - MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. FAU - Yeo, Giles S H AU - Yeo GSH AD - MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK. FAU - Rochford, Justin J AU - Rochford JJ AD - Department of Pharmacology, University of Cambridge, Cambridge, UK. FAU - Garfield, Alastair S AU - Garfield AS AD - Department of Pharmacology, University of Cambridge, Cambridge, UK. FAU - Heisler, Lora K AU - Heisler LK AD - Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK. AD - Department of Pharmacology, University of Cambridge, Cambridge, UK. LA - eng GR - WT098012/WT_/Wellcome Trust/United Kingdom GR - BB/K001418/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - 100574/Z/12/Z/WT_/Wellcome Trust/United Kingdom GR - MRC_MC_UU_12012/5/MRC_/Medical Research Council/United Kingdom GR - MC_UU_00014/5/MRC_/Medical Research Council/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - MC_UU_12012/5/MRC_/Medical Research Council/United Kingdom GR - BB/NO17838/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - 093566/Z/10/A/WT_/Wellcome Trust/United Kingdom GR - MC/PC/15077/MRC_/Medical Research Council/United Kingdom GR - 204815/Z/16/Z/WT_/Wellcome Trust/United Kingdom GR - WT081713/WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Bscl2 protein, mouse) RN - 0 (GTP-Binding Protein gamma Subunits) RN - 0 (NUCB2 protein, human) RN - 0 (Nucleobindins) RN - 0 (Receptors, Leptin) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 66796-54-1 (Pro-Opiomelanocortin) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 9011-97-6 (Cholecystokinin) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type I) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - EC 2.3.1.6 (Choline O-Acetyltransferase) SB - IM MH - Animals MH - Brain Stem/*metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cholecystokinin/metabolism MH - Choline O-Acetyltransferase/metabolism MH - GTP-Binding Protein gamma Subunits/metabolism MH - Glucagon-Like Peptide 1/metabolism MH - Green Fluorescent Proteins/genetics/metabolism MH - Mice MH - Mice, Transgenic MH - Neurons/*metabolism MH - Nitric Oxide Synthase Type I/metabolism MH - Nucleobindins/metabolism MH - Pro-Opiomelanocortin/*metabolism MH - Promoter Regions, Genetic MH - Receptors, Leptin/genetics/*metabolism MH - Tyrosine 3-Monooxygenase/metabolism PMC - PMC7102873 OTO - NOTNLM OT - NTS OT - Pomc OT - leptin receptor OT - obesity EDAT- 2020/03/14 06:00 MHDA- 2020/08/01 06:00 PMCR- 2020/03/13 CRDT- 2020/03/14 06:00 PHST- 2019/10/08 00:00 [received] PHST- 2020/03/10 00:00 [accepted] PHST- 2020/03/14 06:00 [pubmed] PHST- 2020/08/01 06:00 [medline] PHST- 2020/03/14 06:00 [entrez] PHST- 2020/03/13 00:00 [pmc-release] AID - 5804227 [pii] AID - bqaa032 [pii] AID - 10.1210/endocr/bqaa032 [doi] PST - ppublish SO - Endocrinology. 2020 Apr 1;161(4):bqaa032. doi: 10.1210/endocr/bqaa032.