A mouse model for a partially inactive obesity-associated human MC3R variant

Nature Communications
Bonggi LeeJack A Yanovski

Abstract

We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3R(hWT/hWT)) and double-mutant (C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/hDM) have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3R(hWT/hWT). MC3R(hDM/hDM) mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects. MC3R(hDM/hDM) bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3R(hWT/hWT) MSCs. MC3R(hDM/hDM) impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development.

References

Jan 23, 1999·American Journal of Human Genetics·J H LeeR A Price
Apr 2, 1999·Science·M F PittengerD R Marshak
Mar 7, 2000·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·W D LiR A Price
Oct 5, 2001·Nature Reviews. Genetics·N G CopelandD L Court
Feb 21, 2002·Trends in Endocrinology and Metabolism : TEM·Anders H BergPhilipp E Scherer
Mar 13, 2002·The Journal of Clinical Endocrinology and Metabolism·Yung-Seng LeeKah-Yin Loke
Aug 6, 2002·Diabetes Research and Clinical Practice·Jencia WongKathleen G Mountjoy
Jan 18, 2003·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·C Schalin-JänttiK Kontula
Mar 11, 2004·The International Journal of Biochemistry & Cell Biology·C A RoufosseN A Wright
Jan 19, 2005·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·A S LihnB Richelsen
Jan 26, 2006·Peptides·Andrew A Butler
Oct 6, 2006·Obesity·Rexford S Ahima
Jul 20, 2007·Diabetes·Yung Seng LeeKah Yin Loke
Aug 25, 2007·The Journal of Clinical Investigation·Ja-Young KimPhilipp E Scherer
May 27, 2008·Journal of Lipid Research·Vered Elgazar-CarmonRachel Levy
Apr 28, 2009·Journal of Translational Medicine·Neil H RiordanBoris Minev
Apr 28, 2009·La Revue de médecine interne·K Clément, S Vignes
Aug 7, 2009·The American Journal of Clinical Nutrition·David M SavastanoJack A Yanovski
Oct 31, 2009·Arthritis and Rheumatism·Luca Dalle CarbonareVincenzo Lo Cascio
Jan 11, 2011·Nature Medicine·Bolormaa VandanmagsarVishwa Deep Dixit
Feb 8, 2011·Current Opinion in Endocrinology, Diabetes, and Obesity·Guenther Boden
Feb 18, 2011·American Journal of Physiology. Endocrinology and Metabolism·Liping QiaoJianhua Shao
Jun 3, 2011·The Journal of Clinical Investigation·Kai SunPhilipp E Scherer
Feb 14, 2012·Cell Metabolism·Martin G MyersJack A Yanovski
Mar 22, 2012·Obesity Facts·Patrick TarnowHeike Biebermann
May 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Benjamin J RenquistRoger D Cone
Jun 9, 2012·Journal of Applied Physiology·Tara M HenaganLaura K Stewart
Aug 7, 2012·Nature Medicine·Saswata TalukdarJerrold M Olefsky
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Oct 31, 2013·Reviews in Endocrine & Metabolic Disorders·Bonggi Lee, Jianhua Shao
Mar 7, 2015·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Maria E MarketouPanos E Vardas
Jul 21, 2015·Cell Metabolism·Mikael RydénPeter Arner

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Citations

Jul 29, 2016·The New England Journal of Medicine·Marc L Reitman
Oct 8, 2016·Scientific Reports·Panpan YouMingyao Liu
Apr 1, 2017·Frontiers in Neuroscience·Andrew A ButlerSusan A Farr
Aug 18, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·David R PowellRobert Brommage
Apr 4, 2020·Molecular Metabolism·Hui YuMalcolm J Low
Nov 19, 2020·Nutrients·Emanuela Micioni Di BonaventuraCarlo Cifani
Aug 10, 2021·Neuropharmacology·Anna I DuniganAaron G Roseberry

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Methods Mentioned

BETA
PCR
X-ray
fluorescence-activated cell sorting
flow cytometry
transfections

Clinical Trials Mentioned

NCT00001522
NCT00001723

Software Mentioned

GraphPad Prism
Image J
FlowJo
SPSS

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