Impairment of adrenergically-regulated thermogenesis in brown fat of obesity-resistant mice is compensated by non-shivering thermogenesis in skeletal muscle

Janovská, Petra; Zouhar, Petr; Bardová, Kristina; Otáhal, Jakub; Vrbacký, Marek; Mráček, Tomáš; Adamcová, Kateřina; Leňková, Lucie; Funda, Jiří; Čajka, Tomáš; Drahota, Zdeněk; Stanić, Sara; Rustan, A. C.; Horáková, Olga; Houštěk, Josef; Rossmeisl, Martin; Kopecký, Jan

doi:https://dx.doi.org/10.1016/j.molmet.2023.101683

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Impairment of adrenergically-regulated thermogenesis in brown fat of obesity-resistant mice is compensated by non-shivering thermogenesis in skeletal muscle

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SYSNO ASEP	0570490
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Impairment of adrenergically-regulated thermogenesis in brown fat of obesity-resistant mice is compensated by non-shivering thermogenesis in skeletal muscle
Author(s)	Janovská, Petra (FGU-C)_{RID, ORCID} Zouhar, Petr (FGU-C)_{RID, ORCID, SAI} Bardová, Kristina (FGU-C)_{RID, ORCID, SAI} Otáhal, Jakub (FGU-C)_{RID, ORCID, SAI} Vrbacký, Marek (FGU-C)_{RID, ORCID} Mráček, Tomáš (FGU-C)_{RID, ORCID} Adamcová, Kateřina (FGU-C)_{ORCID, RID} Leňková, Lucie (FGU-C)_{ORCID, RID} Funda, Jiří (FGU-C)_ORCID Čajka, Tomáš (FGU-C)_{RID, ORCID, SAI} Drahota, Zdeněk (FGU-C)_{RID, ORCID} Stanić, Sara (FGU-C) Rustan, A. C. (NO) Horáková, Olga (FGU-C)_{RID, ORCID} Houštěk, Josef (FGU-C)_{RID, ORCID} Rossmeisl, Martin (FGU-C)_{RID, ORCID} Kopecký, Jan (FGU-C)_{RID, ORCID}
Article number	101683
Source Title	Molecular Metabolism. - : Elsevier - ISSN 2212-8778 Roč. 69, March (2023)
Number of pages	19 s.
Language	eng - English
Country	NL - Netherlands
Keywords	non-shivering thermogenesis ; sarcolipin ; mitochondrial supercomplex ; skeletal muscle ; brown adipose tissue ; obesity
OECD category	Endocrinology and metabolism (including diabetes, hormones)
R&D Projects	LX22NPO5104 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	GA18-04483S GA ČR - Czech Science Foundation (CSF)
	GA19-02411S GA ČR - Czech Science Foundation (CSF)
	GA21-18993S GA ČR - Czech Science Foundation (CSF)
	GA22-07004S GA ČR - Czech Science Foundation (CSF)
Research Infrastructure	Czech-BioImaging II - 90129 - Ústav molekulární genetiky AV ČR, v. v. i.
Method of publishing	Open access
Institutional support	FGU-C - RVO:67985823
UT WOS	000964009500001
EID SCOPUS	85149068713
DOI	10.1016/j.molmet.2023.101683
Annotation	Objective:Non-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) can be activated via the adrenergic system in response to cold or diet, contributing to both thermal and energy homeostasis. Other mechanisms, including metabolism of skeletal muscle, may also be involved in NST. However, relative contribution of these energy dissipating pathways and their adaptability remain a matter of long-standing controversy.Methods:We used warm-acclimated (30 °C) mice to characterize the effect of an up to 7-day cold acclimation (6 °C, CA) on thermoregulatory thermogenesis, comparing inbred mice with a genetic background conferring resistance (A/J) or susceptibility (C57BL/6 J) to obesity.Results:Both warm-acclimated C57BL/6 J and A/J mice exhibited similar cold endurance, assessed as a capability to maintain core body temperature during acute exposure to cold, which improved in response to CA, resulting in comparable cold endurance and similar induction of UCP1 protein in BAT of mice of both genotypes. Despite this, adrenergic NST in BAT was induced only in C57BL/6 J, not in A/J mice subjected to CA. Cold tolerance phenotype of A/J mice subjected to CA was not based on increased shivering, improved insulation, or changes in physical activity. On the contrary, lipidomic, proteomic and gene expression analyses along with palmitoyl carnitine oxidation and cytochrome c oxidase activity revealed induction of lipid oxidation exclusively in skeletal muscle of A/J mice subjected to CA. These changes appear to be related to skeletal muscle NST, mediated by sarcolipin-induced uncoupling of sarco(endo)plasmic reticulum calcium ATPase pump activity and accentuated by changes in mitochondrial respiratory chain supercomplexes assembly.Conclusions:Our results suggest that NST in skeletal muscle could be adaptively augmented in the face of insufficient adrenergic NST in BAT, depending on the genetic background of the mice. It may provide both protection from cold and resistance to obesity, more effectively than BAT.
Workplace	Institute of Physiology
Contact	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Year of Publishing	2024
Electronic address	https://doi.org/10.1016/j.molmet.2023.101683

Number of the records: 1