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

Autor: Ahmad B; School of Biosciences, Faculty of Health and Medical Sciences Taylor's University Lakeside Campus, No1 Jalan Taylor's, 47500, Subang Jaya, Malaysia., Friar EP; School of Chemistry and Forensic Science, Ingram Building, University of Kent, Canterbury, Kent, CT2 7NH, United Kingdom., Vohra MS; School of Medicine, Faculty of Health and Medical Sciences Taylor's University Lakeside Campus, No1 Jalan Taylor's, 47500, Subang Jaya, Malaysia., Khan N; R3 Medical Research, 10045 East Dynamite Boulevard Suite 260, Scottsdale, AZ, 85262, United States., Serpell CJ; School of Chemistry and Forensic Science, Ingram Building, University of Kent, Canterbury, Kent, CT2 7NH, United Kingdom. Electronic address: C.J.Serpell@kent.ac.uk., Garrett MD; School of Biosciences, Stacey Building, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom., Loo JSE; School of Pharmacy, Faculty of Health and Medical Sciences Taylor's University Lakeside Campus, No1 Jalan Taylor's, 47500, Subang Jaya, Malaysia., Fong IL; Department of Paraclinical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak (UNIMAS), 94300, Kota Samarahan, Sarawak, Malaysia., Wong EH; School of Medicine, Faculty of Health and Medical Sciences Taylor's University Lakeside Campus, No1 Jalan Taylor's, 47500, Subang Jaya, Malaysia. Electronic address: EngHwa.Wong@taylors.edu.my.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2023 Jul 01; Vol. 379, pp. 110503. Date of Electronic Publication: 2023 Apr 19.
DOI: 10.1016/j.cbi.2023.110503
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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