title: Antidiabetic effect of SN158 through PPARα/γ dual activation in ob/ob mice.
abstract: In this study, we aimed to demonstrate the antidiabetic potential of (E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxyphenyl)acryloyl) phenyl)-4-tert-butylbenzamide (SN158) through peroxisome proliferator-activated receptor (PPAR)-α/γ dual activation. SN158 interacted with both PPARα and PPARγ, and increased their transcriptional activities. Simultaneously, SN158 treatment led to an increase in adipogenic differentiation of 3T3-L1 preadipocytes and fatty acid oxidation in hepatocytes. In addition, glucose uptake in myotubes was significantly increased by SN158 treatment. Finally, SN158 significantly lowered the plasma levels of glucose, triglycerides, and free fatty acids in ob/ob mice without severe weight gain and hepatomegaly. These results suggest that SN158 can be useful as a potential therapeutic agent against type 2 diabetes and related metabolic disorders by alleviating glucose and lipid abnormalities.
authors.affiliation: Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, Gangwon-do 25451, Republic of Korea.
authors.forename: Yujung
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China; College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Yongkai
authors.initials: Y
authors.lastname: Cao
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Suresh
authors.initials: S
authors.lastname: Paudel
authors.affiliation: College of Pharmacy, Mokpo National University, Muan 58554, Republic of Korea.
authors.forename: Goo
authors.initials: G
authors.lastname: Yoon
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Cheon
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.affiliation: School of Pharmaceutical Sciences, Key Laboratory of Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Li Tai
authors.initials: LT
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea. Electronic address: yksnbk@sookmyung.ac.kr.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, Gangwon-do 25451, Republic of Korea. Electronic address: snkim@kist.re.kr.
authors.forename: Su-Nam
authors.initials: SN
authors.lastname: Kim
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D052242:Adiponectin / Q000235:genetics; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D047188:Chalcones / Q000008:administration & dosage / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D010088:Oxidoreductases / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists*; D047494:PPAR delta / Q000819:agonists*; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D013237:Stereoisomerism; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic; D014280:Triglycerides / Q000097:blood
chemical_list: D052242:Adiponectin; D001549:Benzamides; D001786:Blood Glucose; D022763:CCAAT-Enhancer-Binding Protein-alpha; D047188:Chalcones; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047494:PPAR delta; D012333:RNA, Messenger; C000617643:SN158 compound; D045162:Thiazolidinediones; D014280:Triglycerides; D010088:Oxidoreductases; C576470:ACOX2 protein, human; C577474:CPT1A protein, human; D002334:Carnitine O-Palmitoyltransferase; D000077205:Pioglitazone
keywords: (E)-N-(4-(3-(5-bromo-4-hydroxy-2-methoxyphenyl)acryloyl)phenyl)-4-tert-butylbenzamide; Insulin sensitivity; PPARα/γ agonist; SN158