Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat
Identifikátory výsledku
Kód výsledku v 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>
Nalezeny alternativní kódy
RIV/67985823:_____/22:00558033
Výsledek na webu
<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>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10406 - Analytical chemistry
Návaznosti výsledku
Projekt
<a href="/cs/project/GA18-04483S" target="_blank" >GA18-04483S: Úloha bílé tukové tkáně v termogenní odpovědi</a><br>
Návaznosti
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Ostatní
Rok uplatnění
2022
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Molecular Metabolism
ISSN
2212-8778
e-ISSN
2212-8778
Svazek periodika
61
Číslo periodika v rámci svazku
July
Stát vydavatele periodika
NL - Nizozemsko
Počet stran výsledku
21
Strana od-do
101499
Kód UT WoS článku
000804540600004
EID výsledku v databázi Scopus
2-s2.0-85129587717