PMID- 28127879
OWN - NLM
STAT- MEDLINE
DCOM- 20170707
LR  - 20220716
IS  - 1930-739X (Electronic)
IS  - 1930-7381 (Linking)
VI  - 25
IP  - 3
DP  - 2017 Mar
TI  - MTCH2 is a conserved regulator of lipid homeostasis.
PG  - 616-625
LID - 10.1002/oby.21751 [doi]
AB  - OBJECTIVE: 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. METHODS: 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. RESULTS: 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. 
      CONCLUSIONS: 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.
CI  - (c) 2017 The Obesity Society.
FAU - Rottiers, Veerle
AU  - Rottiers V
AD  - Department of Molecular Biology and Genetics, Cornell University, Ithaca, New 
      York, USA.
FAU - Francisco, Adam
AU  - Francisco A
AD  - Department of Biomedical Sciences, College of Veterinary Medicine, Cornell 
      University, Ithaca, New York, USA.
FAU - Platov, Michael
AU  - Platov M
AD  - Department of Biomedical Sciences, College of Veterinary Medicine, Cornell 
      University, Ithaca, New York, USA.
FAU - Zaltsman, Yehudit
AU  - Zaltsman Y
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Ruggiero, Antonella
AU  - Ruggiero A
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Lee, Siu Sylvia
AU  - Lee SS
AD  - Department of Molecular Biology and Genetics, Cornell University, Ithaca, New 
      York, USA.
FAU - Gross, Atan
AU  - Gross A
AD  - Department of Biological Regulation, Weizmann Institute of Science, Rehovot, 
      Israel.
FAU - Libert, Sergiy
AU  - Libert S
AD  - Department of Biomedical Sciences, College of Veterinary Medicine, Cornell 
      University, Ithaca, New York, USA.
LA  - eng
GR  - R01 AG060490/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20170127
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 (Carrier Proteins)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mtch2 protein, mouse)
SB  - IM
MH  - Adipocytes/*metabolism
MH  - Animals
MH  - Caenorhabditis elegans
MH  - Carrier Proteins/metabolism
MH  - Diabetes Mellitus, Type 2
MH  - Diet, High-Fat
MH  - Estrogen Receptor alpha/metabolism
MH  - Homeostasis/*genetics
MH  - Lipid Metabolism/*genetics
MH  - Mice
MH  - Mitochondrial Membrane Transport Proteins/genetics/*metabolism
MH  - Obesity/genetics
EDAT- 2017/01/28 06:00
MHDA- 2017/07/08 06:00
CRDT- 2017/01/28 06:00
PHST- 2016/08/01 00:00 [received]
PHST- 2016/11/22 00:00 [revised]
PHST- 2016/11/28 00:00 [accepted]
PHST- 2017/01/28 06:00 [pubmed]
PHST- 2017/07/08 06:00 [medline]
PHST- 2017/01/28 06:00 [entrez]
AID - 10.1002/oby.21751 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2017 Mar;25(3):616-625. doi: 10.1002/oby.21751. Epub 
      2017 Jan 27.