title: MTCH2 is a conserved regulator of lipid homeostasis.
abstract: More than one-third of U.S. adults have obesity, causing an alarming increase in obesity-related comorbidities such as type 2 diabetes. The functional role of mitochondrial carrier homolog 2 (MTCH2), a human obesity-associated gene, in lipid homeostasis was investigated in Caenorhabditis elegans, cell culture, and mice.
  
  
  
  In C. elegans, MTCH2/MTCH-1 was depleted, using RNAi and a genetic mutant, and overexpressed to assess its effect on lipid accumulation. In cells and mice, shRNAs against MTCH2 were used for knockdown and MTCH2 overexpression vectors were used for overexpression to study the role of this gene in fat accumulation.
  
  
  
  MTCH2 knockdown reduced lipid accumulation in adipocyte-like cells in vitro and in C. elegans and mice in vivo. MTCH2 overexpression increased fat accumulation in cell culture, C. elegans, and mice. Acute MTCH2 inhibition reduced fat accumulation in animals subjected to a high-fat diet. Finally, MTCH2 influenced estrogen receptor 1 (ESR1) activity.
  
  
  
  MTCH2 is a conserved regulator of lipid homeostasis. MTCH2 was found to be both required and sufficient for lipid homeostasis shifts, suggesting that pharmacological inhibition of MTCH2 could be therapeutic for treatment of obesity and related disorders. MTCH2 could influence lipid homeostasis through inhibition of ESR1 activity.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
authors.forename: Veerle
authors.initials: V
authors.lastname: Rottiers
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Francisco
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Platov
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Zaltsman
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Antonella
authors.initials: A
authors.lastname: Ruggiero
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA.
authors.forename: Siu Sylvia
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Atan
authors.initials: A
authors.lastname: Gross
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
authors.forename: Sergiy
authors.initials: S
authors.lastname: Libert
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans; D002352:Carrier Proteins / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2; D059305:Diet, High-Fat; D047628:Estrogen Receptor alpha / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics*; D051379:Mice; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D033681:Mitochondrial Membrane Transport Proteins; C550380:Mtch2 protein, mouse