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Choi, Jang Hyun
Lab of Diabetes and Metabolism (LDM)
Research Interests
  • Diabetes, Metabolic Disorders, PPARg, Gene Regulation, Anti-Diabetic Drug

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Identification and Mechanism of 10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors

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Title
Identification and Mechanism of 10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors
Author
Malapaka, Raghu R. V.Khoo, SokKeanZhang, JifengChoi, Jang HyunZhou, X. EdwardXu, YongGong, YinhanLi, JunYong, Eu-LeongChalmers, Michael J.Chang, LinResau, James H.Griffin, Patrick R.Chen, Y. EugeneXu, H. Eric
Issue Date
2012-01
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v.287, no.1, pp.183 - 195
Abstract
Peroxisome proliferator-activated receptors (PPAR alpha, -beta/delta, and -gamma) are a subfamily of nuclear receptors that plays key roles in glucose and lipid metabolism. PPAR gamma is the molecular target of the thiazolidinedione class of antidiabetic drugs that has many side effects. PPAR gamma is also activated by long chain unsaturated or oxidized/nitrated fatty acids, but its relationship with the medium chain fatty acids remains unclear even though the medium chain triglyceride oils have been used to control weight gain and glycemic index. Here, we show that decanoic acid (DA), a 10-carbon fatty acid and a major component of medium chain triglyceride oils, is a direct ligand of PPAR gamma. DA binds and partially activates PPAR gamma without leading to adipogenesis. Crystal structure reveals that DA occupies a novel binding site and only partially stabilizes the AF-2 helix. DA also binds weakly to PPAR alpha and PPAR beta/delta. Treatments with DA and its triglyceride form improve glucose sensitivity and lipid profiles without weight gain in diabetic mice. Together, these results suggest that DA is a modulating ligand for PPARs, and the structure can aid in designing better and safer PPAR gamma-based drugs.
URI
https://scholarworks.unist.ac.kr/handle/201301/7219
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84855286480
DOI
10.1074/jbc.M111.294785
ISSN
0021-9258
Appears in Collections:
BME_Journal Papers
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