MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.994584/full |
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| author | Na-Yeon Kim Chae-Min Lim Hyo-Min Park Jinju Kim Thu-Huyen Pham Young Yang Hee Pom Lee Jin Tae Hong Do-Young Yoon |
| author_facet | Na-Yeon Kim Chae-Min Lim Hyo-Min Park Jinju Kim Thu-Huyen Pham Young Yang Hee Pom Lee Jin Tae Hong Do-Young Yoon |
| author_sort | Na-Yeon Kim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T19:49:42Z |
| format | Article |
| id | doaj.art-fe79fed6028044c98a62b5b2787ad185 |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T19:49:42Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-fe79fed6028044c98a62b5b2787ad1852022-12-22T02:32:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.994584994584MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cellsNa-Yeon Kim0Chae-Min Lim1Hyo-Min Park2Jinju Kim3Thu-Huyen Pham4Young Yang5Hee Pom Lee6Jin Tae Hong7Do-Young Yoon8Department of Bioscience and Biotechnology, Konkuk University, Seoul, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul, KoreaDepartment of Biological Science, Sookmyung Women’s University, Seoul, KoreaCollege of Pharmacy & Medical Research Center, Chungbuk National University, Cheongju, KoreaCollege of Pharmacy & Medical Research Center, Chungbuk National University, Cheongju, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul, KoreaPeroxisome 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.994584/fullMMPPPPARγ agonisttype 2 diabetes treatmentadipogenesisglucose uptake |
| spellingShingle | Na-Yeon Kim Chae-Min Lim Hyo-Min Park Jinju Kim Thu-Huyen Pham Young Yang Hee Pom Lee Jin Tae Hong Do-Young Yoon MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells Frontiers in Pharmacology MMPP PPARγ agonist type 2 diabetes treatment adipogenesis glucose uptake |
| title | MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells |
| title_full | MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells |
| title_fullStr | MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells |
| title_full_unstemmed | MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells |
| title_short | MMPP promotes adipogenesis and glucose uptake via binding to the PPARγ ligand binding domain in 3T3-L1 MBX cells |
| title_sort | mmpp promotes adipogenesis and glucose uptake via binding to the pparγ ligand binding domain in 3t3 l1 mbx cells |
| topic | MMPP PPARγ agonist type 2 diabetes treatment adipogenesis glucose uptake |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.994584/full |
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