Abstract
ObjectiveMetabolic 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.MethodsTransgenic 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.ResultsMimp/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.ConclusionsMimp/Mtch2 alters lipid metabolism and may play a role in the onset of obesity and development of insulin resistance.
Highlights
Overweight and obesity are a major public health problem, often associated with type 2 diabetes [1, 2], the underlying mechanisms are largely unknown [2, 3]
HEK-293T cells, transiently expressing Mimp/Mitochondrial Carrier Homolog 2 (Mtch2)-GFP (Fig 1A) exhibited lower red to green (R/G) fluorescence ratio (Fig 1B and 1C). These results demonstrate that Mimp/Mtch2-GFP retains its activity as it induces substantial depolarization of the mitochondrial potential, in a manner similar to the native Mimp/Mtch2 [4]
Our results demonstrate that Mimp/Mtch2 overexpression leads to fat accumulation in kidneys and livers in mice consuming high fat diet (HFD)
Summary
Metabolic dysfunctions, such as fatty liver, obesity and insulin resistance, are among the most common contemporary diseases worldwide, and their prevalence is continuously rising. Data Availability Statement: Microarray data are available in the ArrayExpress database (www.ebi.ac. uk/arrayexpress) under accession number E-MTAB1752
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