title: Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced Obesity.
abstract: Mitochondrial carrier homolog 2 (MTCH2) is a repressor of mitochondrial oxidative phosphorylation (OXPHOS), and its locus is associated with increased BMI in humans. Here, we demonstrate that mice deficient in muscle MTCH2 are protected from diet-induced obesity and hyperinsulinemia and that they demonstrate increased energy expenditure. Deletion of muscle MTCH2 also increases mitochondrial OXPHOS and mass, triggers conversion from glycolytic to oxidative fibers, increases capacity for endurance exercise, and increases heart function. Moreover, metabolic profiling of mice deficient in muscle MTCH2 reveals a preference for carbohydrate utilization and an increase in mitochondria and glycolytic flux in muscles. Thus, MTCH2 is a critical player in muscle biology, modulating metabolism and mitochondria mass as well as impacting whole-body energy homeostasis.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Buzaglo-Azriel
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Kuperman
authors.affiliation: Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Tsoory
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Zaltsman
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Shachnai
authors.affiliation: Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Smadar Levin
authors.initials: SL
authors.lastname: Zaidman
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Elad
authors.initials: E
authors.lastname: Bassat
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Michailovici
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Alona
authors.initials: A
authors.lastname: Sarver
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eldad
authors.initials: E
authors.lastname: Tzahor
authors.affiliation: Hematology Institute, Kaplan Medical Center, Rehovot 76100, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Haran
authors.affiliation: Cardiovascular, Metabolic, and Endocrine Diseases (CVMED) Research Unit, Pfizer Inc., 610 Main Street, Cambridge, MA 02139, USA.
authors.forename: Cecile
authors.initials: C
authors.lastname: Vernochet
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: atan.gross@weizmann.ac.il.
authors.forename: Atan
authors.initials: A
authors.lastname: Gross
mesh_terms: D000818:Animals; D001823:Body Composition; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004734:Energy Metabolism; D015870:Gene Expression; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D008297:Male; D055442:Metabolome / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000172:deficiency / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010085:Oxidative Phosphorylation; D010805:Physical Conditioning, Animal
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; C550380:Mtch2 protein, mouse