Počet záznamů: 1  

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

  1. 1.
    0558033 - FGÚ 2023 RIV NL eng J - Článek v odborném periodiku
    Oeckl, J. - Janovská, Petra - Adamcová, Kateřina - Bardová, Kristina - Brunner, S. - Dieckmann, S. - Ecker, J. - Fromme, T. - Funda, Jiří - Gantert, T. - Giansanti, P. - Soledad Hidrobo, M. - Kuda, Ondřej - Kuster, B. - Li, Y. - Pohl, Radek - Schmitt, S. - Schweizer, S. - Zischka, H. - Zouhar, Petr - Kopecký, Jan - Klingenspor, M.
    Loss of UCP1 function augments recruitment of futile lipid cycling for thermogenesis in murine brown fat.
    Molecular Metabolism. Roč. 61, July (2022), č. článku 101499. ISSN 2212-8778. E-ISSN 2212-8778
    Grant CEP: GA ČR(CZ) GA18-04483S
    Institucionální podpora: RVO:67985823 ; RVO:61388963
    Klíčová slova: brown adipose tissue * UCP1-independent thermogenesis * futile substrate cycle * lipolysis * re-esterification * fatty acids
    Obor OECD: Endocrinology and metabolism (including diabetes, hormones)
    Impakt faktor: 8.568, rok: 2021
    Způsob publikování: Open access
    https://doi.org/10.1016/j.molmet.2022.101499

    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.
    Trvalý link: http://hdl.handle.net/11104/0331846

     
     
Počet záznamů: 1