Mutant Wars2 gene in spontaneously hypertensive rats impairs brown adipose tissue function and predisposes to visceral obesity

Pravenec, Michal; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šilhavý, Jan; Šimáková, Miroslava; Trnovská, J.; Škop, V.; Marková, I.; Malínská, H.; Hüttl, M.; Kazdová, L.; Bardová, Kristina; Tauchmannová, Kateřina; Vrbacký, Marek; Nůsková, Hana; Mráček, Tomáš; Kopecký, Jan; Houštěk, Josef

doi:https://dx.doi.org/10.33549/physiolres.933811

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Mutant Wars2 gene in spontaneously hypertensive rats impairs brown adipose tissue function and predisposes to visceral obesity

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SYSNO ASEP	0484413
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Mutant Wars2 gene in spontaneously hypertensive rats impairs brown adipose tissue function and predisposes to visceral obesity
Author(s)	Pravenec, Michal (FGU-C)_{RID, ORCID} Zídek, Václav (FGU-C)_RID Landa, Vladimír (FGU-C)_RID Mlejnek, Petr (FGU-C)_{RID, ORCID} Šilhavý, Jan (FGU-C)_{RID, ORCID} Šimáková, Miroslava (FGU-C)_{RID, ORCID} Trnovská, J. (CZ) Škop, V. (CZ) Marková, I. (CZ) Malínská, H. (CZ) Hüttl, M. (CZ) Kazdová, L. (CZ) Bardová, Kristina (FGU-C)_{RID, ORCID, SAI} Tauchmannová, Kateřina (FGU-C)_{RID, ORCID} Vrbacký, Marek (FGU-C)_{RID, ORCID} Nůsková, Hana (FGU-C)_{RID, ORCID} Mráček, Tomáš (FGU-C)_{RID, ORCID} Kopecký, Jan (FGU-C)_{RID, ORCID} Houštěk, Josef (FGU-C)_{RID, ORCID}
Source Title	Physiological Research. - : Fyziologický ústav AV ČR, v. v. i. - ISSN 0862-8408 Roč. 66, č. 6 (2017), s. 917-924
Number of pages	8 s.
Language	eng - English
Country	CZ - Czech Republic
Keywords	brown adipose tissue ; spontaneously hypertensive rat ; quantitative trait loci ; transgenic ; Wars2 gene ; mitochondrial proteosynthesis
Subject RIV	EB - Genetics ; Molecular Biology
OECD category	Endocrinology and metabolism (including diabetes, hormones)
R&D Projects	GA13-04420S GA ČR - Czech Science Foundation (CSF)
Institutional support	FGU-C - RVO:67985823
UT WOS	000419545200002
EID SCOPUS	85039166789
DOI	https://doi.org/10.33549/physiolres.933811
Annotation	Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Identification of genes responsible for BAT function would shed light on underlying pathophysiological mechanisms of metabolic disturbances. Recent linkage analysis in the BXH/HXB recombinant inbred (RI) strains, derived from Brown Norway (BN) and spontaneously hypertensive rats (SHR), identified two closely linked quantitative trait loci (QTL) associated with glucose oxidation and glucose incorporation into BAT lipids in the vicinity of Wars2 (tryptophanyl tRNA synthetase 2 (mitochondrial)) gene on chromosome 2. The SHR harbors L53F WARS2 protein variant that was associated with reduced angiogenesis and Wars2 thus represents a prominent positional candidate gene. In the current study, we validated this candidate as a quantitative trait gene (QTG) using transgenic rescue experiment. SHR-Wars2 transgenic rats with wild type Wars2 gene when compared to SHR, showed more efficient mitochondrial proteosynthesis and increased mitochondrial respiration, which was associated with increased glucose oxidation and incorporation into BAT lipids, and with reduced weight of visceral fat. Correlation analyses in RI strains showed that increased activity of BAT was associated with amelioration of insulin resistance in muscle and white adipose tissue. In summary, these results demonstrate important role of Wars2 gene in regulating BAT function and consequently lipid and glucose metabolism.
Workplace	Institute of Physiology
Contact	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Year of Publishing	2018

Number of the records: 1