UCP1 - a lever of the redox-metabolic seesaw in the regulation of lipid-buffering function of white adipose tissue
2022
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2022 by the Society for Free Radical Research-Europe
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Приказ свих података о документуАпстракт:
Uncoupling protein 1 (UCP1) is a molecular hallmark of thermogenic adipocytes. It can also reside in the unilocular adipocytes of white adipose tissue (WAT) that do not possess almost any oxidation and thermogenesis capacity. Therefore, the significance of UCP1 in WAT is vague. To clarify the physiological role of UCP1 in white adipocytes we aimed to investigate the relation of UCP1 expression with the components of redox-adaptive homeostasis and metabolic function in WAT. Toward this, we investigated the expression pattern of UCP1 with Nrf2 and its downstream targets, glutathione (GSH), and lipid peroxidation levels during extensive lipolysis induced by long-term cold exposure and during reversal, when lipid deposits in adipocytes recover, upon re-acclimation from cold to room temperature (RT). To this end, stated molecular targets were investigated at different time points during 45 days of cold acclimation and re-acclimation in the rat retroperitoneal WAT (rpWAT) and compared to respective RT and cold-acclimated controls. The results have shown that in response to cold-induced lipid mobilization transient induction of UCP1 precedes Nrf2 expression and upregulation of downstream antioxidant enzymes (such as MnSOD and GST). The reverse sequence of molecular events was observed during the early (1-12. days) and late (12-45. days) periods of re-acclimation from cold to RT. Namely, in the initial days of re-acclimation high lipogenesis and redox threshold (GSH, and expression of CuZnSOD and MnSOD) correspond to lower UCP1 levels. From the moment of restitution of lipid reserves (revealed by rpWAT mass) and on, UCP1, GSH, and most antioxidant enzymes return to their RT control values. The results emphasize that UCP1 and Nrf2 represent levers of redox-metabolic seesaw fine-tuning of redox homeostasis for optimal regulation of lipid mobilization and deposition in white adipocytes. Research is supported by the Science Fund of the Republic of Serbia, PROMIS, #6066747-WARMED.
Финансирање / пројекти:
- WARMED - Development of No-Based Approaches for Guided White Adipose Tissue Browning. Can We Tackle Metabolic Diseases By Heating Up/Cooling Down the Fat? (RS-ScienceFundRS-Promis-6066747)
У:
- Redox Biology Congress 2022; 2022 Aug 24-26; Ghent, Belgium. Society for Free Radical Research-Europe; 2022. p. 35. (Free Radical Biology and Medicine; Vol. 189; Suppl. 1).