Loss of transient receptor potential channel 5 causes obesity and postpartum depression.

Autor:	Li Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Cacciottolo TM; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Yin N; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., He Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Jan and Dan Duncan Neurological Research Institute, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA., Liu H; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Liu H; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Yang Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Taizhou People's Hospital, Medical School of Yangzhou University, Taizhou, Jiangsu, China., Henning E; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Keogh JM; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Lawler K; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Mendes de Oliveira E; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Gardner EJ; MRC Epidemiology Unit, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Kentistou KA; MRC Epidemiology Unit, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Laouris P; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Bounds R; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Ong KK; MRC Epidemiology Unit, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Perry JRB; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK; MRC Epidemiology Unit, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK., Barroso I; Exeter Centre of Excellence for Diabetes Research (EXCEED), University of Exeter Medical School, Exeter, UK., Tu L; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Bean JC; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Yu M; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Conde KM; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Wang M; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Ginnard O; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Fang X; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Tong L; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Han J; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Darwich T; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Williams KW; Center for Hypothalamic Research, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9077, USA., Yang Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Wang C; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Joss S; West of Scotland Regional Genetics Service, Queen Elizabeth University Hospital, Glasgow, UK., Firth HV; Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust & Wellcome Sanger Institute, Cambridge, UK., Xu Y; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Department of Medicine, Baylor College of Medicine, Houston, TX, USA. Electronic address: yongx@bcm.edu., Farooqi IS; University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre, Cambridge, UK. Electronic address: isf20@cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Aug 08; Vol. 187 (16), pp. 4176-4192.e17. Date of Electronic Publication: 2024 Jul 02.
DOI:	10.1016/j.cell.2024.06.001
Abstrakt:	Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of Trpc5 from oxytocin neurons in the hypothalamic paraventricular nucleus caused obesity in both sexes and postpartum depressive behavior in females, while Trpc5 overexpression in oxytocin neurons in knock-in mice reversed these phenotypes. We demonstrate that TRPC5 plays a pivotal role in mediating innate human behaviors fundamental to survival, including food seeking and maternal care. Competing Interests: Declaration of interests I.S.F. has consulted for a number of companies developing weight loss drugs (including Eli Lilly, Novo Nordisk, and Rhythm Pharmaceuticals) and investors (Goldman Sachs, SV Health). I.S.F. is a member of the Advisory Board of Cell. J.R.B.P. is an employee and shareholder of Insmed, receives research funding from GSK, and is a paid consultant for WW International. K.W.W. holds shares in Novo Nordisk and Eli Lilly. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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