Author:
Kim Na-Yeon,Lim Chae-Min,Park Hyo-Min,Kim Jinju,Pham Thu-Huyen,Yang Young,Lee Hee Pom,Hong Jin Tae,Yoon Do-Young
Abstract
Peroxisome proliferator-activated receptor-gamma (PPARγ) is a transcription factor involved in adipogenesis, and its transcriptional activity depends on its ligands. Thiazolidinediones (TZDs), well-known PPARγ agonists, are drugs that improve insulin resistance in type 2 diabetes. However, TZDs are associated with severe adverse effects. As current therapies are not well designed, novel PPARγ agonists have been investigated in adipocytes. (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) is known to have anti-arthritic, anti-inflammatory, and anti-cancer effects. In this study, we demonstrated the adipogenic effects of MMPP on the regulation of PPARγ transcriptional activity during adipocyte differentiation in vitro. MMPP treatment increased PPARγ transcriptional activity, and molecular docking studies revealed that MMPP binds directly to the PPARγ ligand binding domain. MMPP and rosiglitazone showed similar binding affinities to the PPARγ. MMPP significantly promoted lipid accumulation in adipocyte cells and increased the expression of C/EBPβ and the levels of p-AKT, p-GSK3, and p-AMPKα at an early stage. MMPP enhanced the expression of adipogenic markers such as PPARγ, C/EBPα, FAS, ACC, GLUT4, FABP4 and adiponectin in the late stage. MMPP also improved insulin sensitivity by increasing glucose uptake. Thus, MMPP, as a PPARγ agonist, may be a potential drug for type 2 diabetes and metabolic disorders, which may help increase adipogenesis and insulin sensitivity.
Funder
National Research Foundation of Korea
Konkuk University
Subject
Pharmacology (medical),Pharmacology
Reference47 articles.
1. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction;Achari;Int. J. Mol. Sci.,2017
2. Type III collagen is required for adipogenesis and actin stress fibre formation in 3T3-L1 preadipocytes;Al Hasan;Biomolecules,2021
3. Transcriptional regulation of metabolic pathways via lipid-sensing nuclear receptors PPARs, FXR, and LXR in NASH;Cariello;Cell. Mol. Gastroenterol. Hepatol.,2021
4. Natural products and obesity: A focus on the regulation of mitotic clonal expansion during adipogenesis;Chang;Molecules,2019
5. The DPA-derivative 11S, 17S-dihydroxy 7, 9, 13, 15, 19 (Z, E, Z, E, Z)-docosapentaenoic acid inhibits IL-6 production by inhibiting ROS production and ERK/NF-κB pathway in keratinocytes HaCaT stimulated with a fine dust PM10;Choi;Ecotoxicol. Environ. Saf.,2022