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Hydroxylated polymethoxyflavones reduce the activity of pancreatic lipase, inhibit adipogenesis and enhance lipolysis in 3T3-L1 mouse embryonic fibroblast cells

Ahmad, Bilal, Friar, Emily P., Vohra, Muhammad Sufyan, Khan, Nasar, Serpell, Christopher J., Garrett, Michelle D., Loo, Jason Siau Ee, Fong, Isabel Lim, Wong, Eng Hwa (2023) Hydroxylated polymethoxyflavones reduce the activity of pancreatic lipase, inhibit adipogenesis and enhance lipolysis in 3T3-L1 mouse embryonic fibroblast cells. Chemico-Biological Interactions, 379 . Article Number 110503. ISSN 0009-2797. (doi:10.1016/j.cbi.2023.110503) (KAR id:101195)

Abstract

Hydroxylated polymethoxyflavones (HPMFs) have been shown to possess various anti-disease effects, including against obesity. This study investigates the anti-obesity effects of HPMFs in further detail, aiming to gain understanding of their mechanism of action in this context. The current study demonstrates that two HPMFs; 3′-hydroxy-5,7,4′,5′-tetramethoxyflavone (3′OH-TetMF) and 4′-hydroxy-5,7,3′,5′-tetramethoxyflavone (4′OH-TetMF) possess anti-obesity effects. They both significantly reduced pancreatic lipase activity in a competitive manner as demonstrated by molecular docking and kinetic studies. In cell studies, it was revealed that both of the HPMFs suppress differentiation of 3T3-L1 mouse embryonic fibroblast cells during the early stages of adipogenesis. They also reduced expression of key adipogenic and lipogenic marker genes, namely peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), adipocyte binding protein 2 (aP2), fatty acid synthase (FASN), and sterol regulatory element-binding protein 1 (SREBF 1). They also enhanced the expression of cell cycle genes, i.e., cyclin D1 (CCND1) and C-Myc, and reduced cyclin A2 expression. When further investigated, it was also observed that these HPMFs accelerate lipid breakdown (lipolysis) and enhance lipolytic genes expression. Moreover, they also reduced the secretion of proteins (adipokines), including pro-inflammatory cytokines, from mature adipocytes. Taken together, this study concludes that these HPMFs have anti-obesity effects, which are worthy of further investigation.

Item Type: Article
DOI/Identification number: 10.1016/j.cbi.2023.110503
Uncontrolled keywords: HPMFs, Pancreatic lipase, Obesity, Lipolysis, 3T3-L1 adipocytes
Subjects: Q Science
Q Science > QD Chemistry
Divisions: Divisions > Division of Natural Sciences > Chemistry and Forensics
Funders: Engineering and Physical Sciences Research Council (https://ror.org/0439y7842)
University of Kent (https://ror.org/00xkeyj56)
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 12 May 2023 14:16 UTC
Last Modified: 15 May 2023 11:36 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/101195 (The current URI for this page, for reference purposes)

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