Potent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice.
Peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists have been developed to alleviate metabolic disorders and have the potential to be used as therapeutic agents for the treatment of type 2 diabetes. In this study, we investigated the effects of a newly synthesized PPAR α/γ dual agoni...
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oai:doaj.org-article:d41df04f737e4e5584b10e4c0ef5c9222021-11-18T08:46:36ZPotent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice.1932-620310.1371/journal.pone.0078815https://doaj.org/article/d41df04f737e4e5584b10e4c0ef5c9222013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24244369/?tool=EBIhttps://doaj.org/toc/1932-6203Peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists have been developed to alleviate metabolic disorders and have the potential to be used as therapeutic agents for the treatment of type 2 diabetes. In this study, we investigated the effects of a newly synthesized PPAR α/γ dual agonist, 2-[4-(5-chlorobenzo [d] thiazol-2-yl) phenoxy]-2-methylpropanoic acid (MHY908) on type 2 diabetes in vitro and in vivo. To obtain initial evidence that MHY908 acts as a PPAR α/γ dual agonist, ChIP and reporter gene assays were conducted in AC2F rat liver cells, and to investigate the anti-diabetic effects and molecular mechanisms, eight-week-old, male db/db mice were allowed to eat ad libitum, placed on calorie restriction, or administered MHY908 (1 mg or 3 mg/kg/day) mixed in food for 4 weeks. Age-matched male db/m lean mice served as non-diabetic controls. It was found that MHY908 enhanced the binding and transcriptional activity of PPAR α and γ in AC2F cells, and it reduced serum glucose, triglyceride, and insulin levels, however increased adiponectin levels without body weight gain. In addition, MHY908 significantly improved hepatic steatosis by enhancing CPT-1 levels. Remarkably, MHY908 reduced endoplasmic reticulum (ER) stress and c-Jun N-terminal kinase (JNK) activation in the livers of db/db mice, and subsequently reduced insulin resistance. The study shows MHY908 has beneficial effects on type 2 diabetes by simultaneously activating PPAR α/γ and improving ER stress, and suggests that MHY908 could have a potent anti-diabetic effect as a PPAR α/γ dual agonist, and potential for the treatment of type 2 diabetes.Min Hi ParkJi Young ParkHye Jin LeeDae Hyun KimDaeui ParkHyoung Oh JeongChan Hum ParkPusoon ChunHyung Ryong MoonHae Young ChungPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e78815 (2013) |
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Medicine R Science Q Min Hi Park Ji Young Park Hye Jin Lee Dae Hyun Kim Daeui Park Hyoung Oh Jeong Chan Hum Park Pusoon Chun Hyung Ryong Moon Hae Young Chung Potent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice. |
| description |
Peroxisome proliferator-activated receptor (PPAR) α/γ dual agonists have been developed to alleviate metabolic disorders and have the potential to be used as therapeutic agents for the treatment of type 2 diabetes. In this study, we investigated the effects of a newly synthesized PPAR α/γ dual agonist, 2-[4-(5-chlorobenzo [d] thiazol-2-yl) phenoxy]-2-methylpropanoic acid (MHY908) on type 2 diabetes in vitro and in vivo. To obtain initial evidence that MHY908 acts as a PPAR α/γ dual agonist, ChIP and reporter gene assays were conducted in AC2F rat liver cells, and to investigate the anti-diabetic effects and molecular mechanisms, eight-week-old, male db/db mice were allowed to eat ad libitum, placed on calorie restriction, or administered MHY908 (1 mg or 3 mg/kg/day) mixed in food for 4 weeks. Age-matched male db/m lean mice served as non-diabetic controls. It was found that MHY908 enhanced the binding and transcriptional activity of PPAR α and γ in AC2F cells, and it reduced serum glucose, triglyceride, and insulin levels, however increased adiponectin levels without body weight gain. In addition, MHY908 significantly improved hepatic steatosis by enhancing CPT-1 levels. Remarkably, MHY908 reduced endoplasmic reticulum (ER) stress and c-Jun N-terminal kinase (JNK) activation in the livers of db/db mice, and subsequently reduced insulin resistance. The study shows MHY908 has beneficial effects on type 2 diabetes by simultaneously activating PPAR α/γ and improving ER stress, and suggests that MHY908 could have a potent anti-diabetic effect as a PPAR α/γ dual agonist, and potential for the treatment of type 2 diabetes. |
| format |
article |
| author |
Min Hi Park Ji Young Park Hye Jin Lee Dae Hyun Kim Daeui Park Hyoung Oh Jeong Chan Hum Park Pusoon Chun Hyung Ryong Moon Hae Young Chung |
| author_facet |
Min Hi Park Ji Young Park Hye Jin Lee Dae Hyun Kim Daeui Park Hyoung Oh Jeong Chan Hum Park Pusoon Chun Hyung Ryong Moon Hae Young Chung |
| author_sort |
Min Hi Park |
| title |
Potent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice. |
| title_short |
Potent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice. |
| title_full |
Potent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice. |
| title_fullStr |
Potent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice. |
| title_full_unstemmed |
Potent anti-diabetic effects of MHY908, a newly synthesized PPAR α/γ dual agonist in db/db mice. |
| title_sort |
potent anti-diabetic effects of mhy908, a newly synthesized ppar α/γ dual agonist in db/db mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/d41df04f737e4e5584b10e4c0ef5c922 |
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