Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00558033" target="_blank" >RIV/61388963:_____/22:00558033 - isvavai.cz</a>

Alternative codes found

RIV/67985823:_____/22:00558033

Result on the web

<a href="https://doi.org/10.1016/j.molmet.2022.101499" target="_blank" >https://doi.org/10.1016/j.molmet.2022.101499</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.molmet.2022.101499" target="_blank" >10.1016/j.molmet.2022.101499</a>

Result language

angličtina

Original language name

Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat

Original language description

Objective:Classical ATP-independent non-shivering thermogenesis enabled by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) is activated, but not essential for survival, in the cold. It has long been suspected that futile ATP-consuming substrate cycles also contribute to thermogenesis and can partially compensate for the genetic ablation of UCP1 in mouse models. Futile ATP-dependent thermogenesis could thereby enable survival in the cold even when brown fat is less abundant or missing.Methods:In this study, we explore different potential sources of UCP1-independent thermogenesis and identify a futile ATP-consuming triglyceride/fatty acid cycle as the main contributor to cellular heat production in brown adipocytes lacking UCP1. We uncover the mechanism on a molecular level and pinpoint the key enzymes involved using pharmacological and genetic interference.Results:ATGL is the most important lipase in terms of releasing fatty acids from lipid droplets, while DGAT1 accounts for the majority of fatty acid re-esterification in UCP1-ablated brown adipocytes. Furthermore, we demonstrate that chronic cold exposure causes a pronounced remodeling of adipose tissues and leads to the recruitment of lipid cycling capacity specifically in BAT of UCP1-knockout mice, possibly fueled by fatty acids from white fat. Quantification of triglyceride/fatty acid cycling clearly shows that UCP1-ablated animals significantly increase turnover rates at room temperature and below.Conclusion:Our results suggest an important role for futile lipid cycling in adaptive thermogenesis and total energy expenditure.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10406 - Analytical chemistry

Project

<a href="/en/project/GA18-04483S" target="_blank" >GA18-04483S: Role of white adipose tissue in the thernogenic response</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Molecular Metabolism

ISSN

2212-8778

e-ISSN

2212-8778

Volume of the periodical

61

Issue of the periodical within the volume

July

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

21

Pages from-to

101499

UT code for WoS article

000804540600004

EID of the result in the Scopus database

2-s2.0-85129587717