Identification and Mechanism of 10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors
文献类型：期刊论文
| 作者 | Malapaka, Raghu R. V.1; Khoo, SokKean2,3; Zhang, Jifeng4; Choi, Jang H.5,6; Zhou, X. Edward1; Xu, Yong1; Gong, Yinhan7; Li, Jun7 ; Yong, Eu-Leong7; Chalmers, Michael J.8
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| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2012-01-02 |
| 卷号 | 287期号:1页码:183-195 |
| ISSN号 | 0021-9258 |
| DOI | 10.1074/jbc.M111.294785 |
| 文献子类 | Article |
| 英文摘要 | 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. |
| WOS关键词 | LONG-CHAIN TRIGLYCERIDES ; WEIGHT-LOSS DIET ; PPAR-GAMMA ; ADIPOCYTE DIFFERENTIATION ; BINDING SELECTIVITY ; NUCLEAR RECEPTORS ; LIPID-METABOLISM ; GENE-EXPRESSION ; RISK-FACTORS ; OLIVE OIL |
| 资助项目 | National Institutes of Health[DK071662] ; National Institutes of Health[DK066202] ; National Institutes of Health[HL089301] ; National Institutes of Health[HL68878] ; National Institutes of Health[HL089544] ; American Heart Association[0835237N] ; American Heart Association[0840025N] ; Jay and Betty Van Andel Foundation, Amway (China) Ltd.[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:000298682400020 |
| 出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278225]  |
| 专题 | 药物靶标结构与功能中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Malapaka, Raghu R. V. |
| 作者单位 | 1.Van Andel Res Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA; 2.Van Andel Res Inst, Lab Microarray Technol, Grand Rapids, MI 49503 USA; 3.Van Andel Res Inst, Lab Analyt Cellular & Mol Microscopy, Grand Rapids, MI 49503 USA; 4.Univ Michigan, Dept Internal Med, Ctr Cardiovasc, Ann Arbor, MI 48109 USA; 5.Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA; 6.Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA; 7.Natl Univ Singapore, Dept Obstet & Gynaecol, Singapore 119228, Singapore; 8.Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA; 9.Chinese Acad Sci, VARI SIMM Ctr Drug Discovery, Ctr Struct & Funct Drug Targets, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Malapaka, Raghu R. V.,Khoo, SokKean,Zhang, Jifeng,et al. Identification and Mechanism of 10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(1):183-195. |
| APA | Malapaka, Raghu R. V..,Khoo, SokKean.,Zhang, Jifeng.,Choi, Jang H..,Zhou, X. Edward.,...&Xu, H. Eric.(2012).Identification and Mechanism of 10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors.JOURNAL OF BIOLOGICAL CHEMISTRY,287(1),183-195. |
| MLA | Malapaka, Raghu R. V.,et al."Identification and Mechanism of 10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors".JOURNAL OF BIOLOGICAL CHEMISTRY 287.1(2012):183-195. |
入库方式： OAI收割
来源：上海药物研究所
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