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MTCH2 is a conserved regulator of lipid homeostasis
- Source :
- Obesity. 25:616-625
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Genetics
Gene knockdown
Nutrition and Dietetics
Endocrinology, Diabetes and Metabolism
Mutant
Regulator
Medicine (miscellaneous)
Biology
biology.organism_classification
Cell biology
03 medical and health sciences
030104 developmental biology
Endocrinology
RNA interference
Cell culture
Mitochondrial Carrier Homolog 2
Estrogen receptor alpha
Caenorhabditis elegans
Subjects
Details
- ISSN :
- 19307381
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Obesity
- Accession number :
- edsair.doi...........a2fca231c03dd87179160b89f509b8d1
- Full Text :
- https://doi.org/10.1002/oby.21751