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Heterozygous Nme7 Mutation Affects Glucose Tolerance in Male Rats
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SYSNO ASEP 0555570 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Heterozygous Nme7 Mutation Affects Glucose Tolerance in Male Rats Author(s) Šedová, Lucie (UMG-J)
Procházka, Jan (UMG-J) ORCID
Zudová, Dagmar (UMG-J)
Bendlová, B. (CZ)
Včelák, J. (CZ)
Sedláček, Radislav (UMG-J) RID
Šeda, O. (CZ)Number of authors 7 Article number 1087 Source Title Genes. - : MDPI
Roč. 12, č. 7 (2021)Number of pages 13 s. Publication form Online - E Language eng - English Country CH - Switzerland Keywords metabolic syndrome ; pancreatic fibrosis ; animal models Subject RIV EB - Genetics ; Molecular Biology OECD category Genetics and heredity (medical genetics to be 3) R&D Projects GA17-13491S GA ČR - Czech Science Foundation (CSF) LM2018126 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED2.1.00/19.0395 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Research Infrastructure CCP II - 90126 - Ústav molekulární genetiky AV ČR, v. v. i. Method of publishing Open access Institutional support UMG-J - RVO:68378050 UT WOS 000677189200001 DOI 10.3390/genes12071087 Annotation Complex metabolic conditions such as type 2 diabetes and obesity result from the interaction of numerous genetic and environmental factors. While the family of Nme proteins has been connected so far mostly to development, proliferation, or ciliary functions, several lines of evidence from human and experimental studies point to the potential involvement of one of its members, NME7 (non-metastatic cells 7, nucleoside diphosphate kinase 7) in carbohydrate and lipid metabolism. As a complete lack of Nme7 is semilethal in rats, we compared morphometric, metabolic, and transcriptomic profiles of standard diet-fed heterozygous Nme7+/- on male rats vs. their wild-type Nme7+/+ controls. Nme7+/- animals showed increased body weight, adiposity, higher insulin levels together with decreased glucose tolerance. Moreover, they displayed pancreatic islet fibrosis and kidney tubular damage. Despite no signs of overt liver steatosis or dyslipidemia, we found significant changes in the hepatic transcriptome of Nme7+/- male rats with a concerted increase of expression of lipogenic enzymes including Scd1, Fads1, Dhcr7 and a decrease of Cyp7b1 and Nme7. Network analyses suggested possible links between Nme7 and the activation of Srebf1 and Srebf2 upstream regulators. These results further support the implication of NME7 in the pathogenesis of glucose intolerance and adiposity. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2022 Electronic address https://www.mdpi.com/2073-4425/12/7/1087
Number of the records: 1