HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

KR-62980 suppresses lipid metabolism through inhibition of cytosolic NADP isocitrate dehydrogenase in zebrafish.

Abstract
Peroxisome proliferator-activated receptor γ (PPARγ) is a target of antidiabetic drugs. However, many PPARγ activators, including rosiglitazone, show unwanted side effects, such as weight gain. The KR-62980 [1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carboxylic acid ethyl ester], a novel partial agonist of PPARγ, is a new compound for diabetes with antihyperglycemic activity and weak antiadipogenic activity. This study was performed to elucidate the mechanism of the weak adipogenesis induced by KR-62980 despite its being a PPARγ agonist in zebrafish. We elucidated the mechanism of KR-62980 in lipid metabolism using adipocytes and zebrafish. Since NADPH is a critical cofactor in fat metabolism, we investigated effect of KR-62980 on NADPH-producing enzymes such as cytosolic NADP(+) isocitrate dehydrogenase (cICDH). We found that the mRNA expression of cICDH was significantly decreased by KR-62980 in 3T3-L1 cells. KR-62980 inhibited lipase activity and lipid metabolism in zebrafish. Further, KR-62980 substantially suppressed cICDH in adipocytes and zebrafish. These results suggest that cICDH may be one of the targets of KR-62980 responsible for weight gain and adipogenesis.
AuthorsHang-Suk Chun, Sun Hye Shin, Sunjoo Ahn, Dae-Seop Shin, Sun-Sil Choi, Jin Hee Ahn, Myung Ae Bae
JournalZebrafish (Zebrafish) Vol. 11 Issue 2 Pg. 122-8 (Apr 2014) ISSN: 1557-8542 [Electronic] United States
PMID24588364 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 1-(methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-1H-indene-2-carboxylic acid ethyl ester
  • Indenes
  • Morpholines
  • PPAR gamma
  • RNA, Messenger
  • Isocitrate Dehydrogenase
  • isocitrate dehydrogenase (NADP+)
Topics
  • 3T3-L1 Cells
  • Animals
  • Cell Line
  • Gene Expression (drug effects)
  • Indenes (pharmacology)
  • Isocitrate Dehydrogenase (genetics, metabolism)
  • Lipid Metabolism (drug effects)
  • Mice
  • Morpholines (pharmacology)
  • PPAR gamma (agonists)
  • Polymerase Chain Reaction
  • RNA, Messenger (genetics, metabolism)
  • Zebrafish (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: