Mimp/Mtch2, an Obesity Susceptibility Gene, Induces Alteration of Fatty Acid Metabolism in Transgenic Mice

• Published in: PloS one Vol. 11; no. 6; p. e0157850
• Main Authors: Bar-Lev, Yamit, Moshitch-Moshkovitz, Sharon, Tsarfaty, Galia, Kaufman, Dafna, Horev, Judith, Resau, James H, Tsarfaty, Ilan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.06.2016; Public Library of Science (PLoS)
• Subjects: Accumulation; Animals; Biology and Life Sciences; Blood; Blood glucose; Blood Glucose - metabolism; Depolarization; Diet, High-Fat; Disease susceptibility; Fatty Acid Synthases - genetics; Fatty acid synthesis; Fatty acids; Fatty liver; Fatty-acid synthase; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation; Genes; Genetic aspects; Genetic engineering; Glucose; High fat diet; Homology; Hyperglycemia; In vivo methods and tests; Insulin; Insulin resistance; Kidney - metabolism; Kidney - pathology; Kidneys; Kinases; Lipid Metabolism; Liver; Liver - metabolism; Liver - pathology; Medicine and Health Sciences; Membrane Potential, Mitochondrial; Metabolism; Mice; Mice, Transgenic; Mitochondria; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Membrane Transport Proteins - metabolism; Muscles; Obesity; Obesity - genetics; Oligonucleotide Array Sequence Analysis - methods; Oxidation; Polymorphism; Research and Analysis Methods; Rodents; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Transgenic mice; Type 2 diabetes; Israel; Tel Aviv Israel; United States > US; Germany; Michigan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0157850

Metabolic dysfunctions, such as fatty liver, obesity and insulin resistance, are among the most common contemporary diseases worldwide, and their prevalence is continuously rising. Mimp/Mtch2 is a mitochondrial carrier protein homologue, which localizes to the mitochondria and induces mitochondrial depolarization. Mimp/Mtch2 single-nucleotide polymorphism is associated with obesity in humans and its loss in mice muscle protects from obesity. Our aim was to study the effects of Mimp/Mtch2 overexpression in vivo. Transgenic mice overexpressing Mimp/Mtch2-GFP were characterized and monitored for lipid accumulation, weight and blood glucose levels. Transgenic mice liver and kidneys were used for gene expression analysis. Mimp/Mtch2-GFP transgenic mice express high levels of fatty acid synthase and of β-oxidation genes and develop fatty livers and kidneys. Moreover, high-fat diet-fed Mimp/Mtch2 mice exhibit high blood glucose levels. Our results also show that Mimp/Mtch2 is involved in lipid accumulation and uptake in cells and perhaps in human obesity. Mimp/Mtch2 alters lipid metabolism and may play a role in the onset of obesity and development of insulin resistance.