@conference{
author = "Zakić, Tamara and Ninković, Anastasija and Stojanović, Sara and Budnar Šoškić, Marta and Kalezić, Anđelika and Janković, Aleksandra and Korać, Aleksandra and Peković-Vaughan, Vanja and Korać, Bato",
year = "2022",
abstract = "Interscapular brown adipose tissue (IBAT) is a highly metabolically active, thermogenic tissue essential for the maintenance of total energy homeostasis, with a remarkable ability for remodelling in response to exogenous stimuli. Given that nuclear factor erythroid 2-related factor 2 (NRF2) has a pivotal role in redox-metabolic homeostasis, we aimed to investigate its role in IBAT homeostasis under basal conditions or upon cold stimulation. Therefore, we analysed structural and redox-metabolic profiles of IBAT in wild-type (WT) and mice lacking functional Nrf2 (Nrf2KO) maintained at room (RT, 24±1°C) or low temperature (4±1°C). Our results show that both WT and Nrf2KO mice appear to be acclimated to cold, showing characteristics of thermogenically active IBAT, including increased gene and protein expression of uncoupling protein 1 (UCP1). Surprisingly, light and electron microscopy revealed that Nrf2KO mice at RT displayed distinct structural features of activated IBAT, together with the presence of vasodilated blood vessels, while the expression of thermogenic marker UCP1 did not show a corresponding cold-induced change, thus indicating IBAT functional inactivity. This lack of IBAT thermogenic activity in Nrf2KO mice at RT is consistent with its altered redox-metabolic profile, whereby protein expression of the main antioxidant defence and key metabolic enzymes either remained the same or was decreased compared to WT mice at RT. Accordingly, circulatory levels of triglycerides and cholesterol were decreased while glucose, urea and creatinine remained unchanged. Moreover, gene and/or protein expression of important redox-metabolic transcriptional factors – erythroid NRF1, NFkB, PGC-1α and PPARγ, as well as eNOS and AMPKα were increased, suggesting compensatory molecular mechanisms leading to altered IBAT phenotype in Nrf2KO mice at RT. In conclusion, the lack of functional Nrf2 leads to marked structural characteristics of active IBAT in Nrf2KO mice at RT, which are only followed by its functional activation through distinct redox-metabolic reprogramming after cold stimulation.",
publisher = "Society for Free Radical Research-Europe",
journal = "Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium",
title = "Structural and redox-metabolic remodelling of brown adipose tissue in mice lacking nuclear factor erythroid 2-related factor 2 under basal conditions and cold acclimation",
doi = "10.1016/j.freeradbiomed.2022.06.035",
pages = "5"
}
