PUBLICATION
KR-62980 Suppresses Lipid Metabolism Through Inhibition of Cytosolic NADP Isocitrate Dehydrogenase in Zebrafish
- Authors
- Chun, H.S., Shin, S.H., Ahn, S., Shin, D.S., Choi, S.S., Ahn, J.H., Bae, M.A.
- ID
- ZDB-PUB-140513-431
- Date
- 2014
- Source
- Zebrafish 11: 122-8 (Journal)
- Registered Authors
- Chun, Hang-Suk
- Keywords
- none
- MeSH Terms
-
- 3T3-L1 Cells
- Animals
- Cell Line
- Gene Expression/drug effects*
- Indenes/pharmacology*
- Isocitrate Dehydrogenase/genetics*
- Isocitrate Dehydrogenase/metabolism
- Lipid Metabolism/drug effects*
- Mice
- Morpholines/pharmacology*
- PPAR gamma/agonists
- Polymerase Chain Reaction
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Zebrafish/genetics*
- Zebrafish/metabolism*
- PubMed
- 24588364 Full text @ Zebrafish
Citation
Chun, H.S., Shin, S.H., Ahn, S., Shin, D.S., Choi, S.S., Ahn, J.H., Bae, M.A. (2014) KR-62980 Suppresses Lipid Metabolism Through Inhibition of Cytosolic NADP Isocitrate Dehydrogenase in Zebrafish. Zebrafish. 11:122-8.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping