Mitochondrial oxidative phosphorylation is impaired in TALLYHO mice, a new obesity and type 2 diabetes animal model

Autor: Emine C. Koc, Jung Han Kim, James Denvir, Zeynep C. Koc, Funda Kartal, Tamara Murphy, Caroline A. Hunter
Přispěvatelé: Ege Üniversitesi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Int J Biochem Cell Biol
ISSN: 3396-0437
Popis: WOS: 000495487400008
PubMed: 31542429
Type 2 diabetes has become an epidemic disease largely explained by the dramatic increase in obesity in recent years. Mitochondrial dysfunction is suggested as an underlying factor in obesity and type 2 diabetes. in this study, we evaluated changes in oxidative phosphorylation and mitochondrial biogenesis in a new human obesity and type 2 diabetes model, TALLYHO/Jng mice. We hypothesized that the sequence variants identified in the whole genome analysis of TALLYHO/Jng mice would affect oxidative phosphorylation and contribute to obesity and insulin resistant phenotypes. To test this hypothesis, we investigated differences in the expression and activity of oxidative phosphorylation complexes, including the transcription and translation of nuclear- and mitochondrial-encoded subunits and enzymatic activities, in the liver and kidney of TALLYHO/Jng and C57BL/6 J mice. A significant decrease was observed in the expression of nuclear- and mitochondrial-encoded subunits of complex I and IV, respectively, in TALLYHO/Jng mice, which coincided with significant reductions in their enzymatic activities. Furthermore, sequence variants were identified in oxidative phosphorylation complex subunits, a mitochondrial tRNA synthetase, and mitochondrial ribosomal proteins. Our data suggested that the lower expression and activity of oxidative phosphorylation complexes results in the diminished energy metabolism observed in TALLYHO/Jng mice. Sequence variants identified in mitochondrial proteins accentuated a defect in mitochondrial protein synthesis which also contributes to impaired biogenesis and oxidative phosphorylation in TALLYHO/Jng mice. These results demonstrated that the identification of factors contributing to mitochondrial dysfunction will allow us to improve the disease prognosis and treatment of obesity and type 2 diabetes in humans.
National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [GM071034, 1 R15 DK113604-01A1]; NASA WV Space Grant Consortium by NASA Goddard Space Flight Center [NNG05GF80H]; WV-INBRE grant [P20GM103434]; WV-CTSI grant [2U54GM104942]; COBRE ACCORD grant [1P20GM121299]; American Heart AssociationAmerican Heart Association [18AIREA33960437]; NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) [R15DK113604] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [P20GM103434, U54GM104942, U54GM104942, P20GM103434, P20GM103434, P20GM103434, P20GM121299, P20GM121299, U54GM104942, U54GM104942, U54GM104942, U54GM104942, P20GM103434, U54GM104942, U54GM104942, P20GM121299, P20GM103434, U54GM104942, U54GM104942, U54GM104942, P20GM121299, P20GM103434, U54GM104942, U54GM104942, U54GM104942, U54GM104942, U54GM104942, P20GM103434, P20GM121299, P20GM103434, P20GM121299, P20GM121299, U54GM104942, P20GM103434, P20GM103434, P20GM121299, P20GM121299, U54GM104942, P20GM121299, P20GM103434, P20GM103434, U54GM104942, P20GM121299, P20GM121299, P20GM121299, P20GM121299, U54GM104942, P20GM103434, U54GM104942, P20GM103434, U54GM104942, P20GM121299, U54GM104942, P20GM103434, U54GM104942, U54GM104942, P20GM103434, P20GM121299, U54GM104942, P20GM121299, U54GM104942, P20GM121299, P20GM121299, P20GM121299, P20GM121299, U54GM104942, U54GM104942, P20GM121299, P20GM103434, U54GM104942, U54GM104942, U54GM104942, P20GM121299, U54GM104942, U54GM104942, P20GM103434] Funding Source: NIH RePORTER
This work was partly supported by National Institutes of Health to ECK [GM071034] and NASA WV Space Grant Consortium issued by NASA Goddard Space Flight Center [NNG05GF80H]. the GABC is supported by the WV-INBRE [P20GM103434], WV-CTSI [2U54GM104942], and the COBRE ACCORD [1P20GM121299] grants. JHK is funded by National Institutes of Health [1 R15 DK113604-01A1] and American Heart Association [18AIREA33960437].
Databáze: OpenAIRE
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