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  • 02월 22일 15시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

Ligands of the Nuclear Receptor PPARδ, Spears in the Heart of Metabolic Syndrome

등록일
2008년 2월 19일 09시 48분 50초
접수번호
1456
발표코드
목17D6심 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
목 16시 : 15분
발표형식
심포지엄
발표분야
생명화학 - Understanding of Metabolic Diseases
저자 및
공동저자
진정욱, 함정엽, 고재영, 양인호, 한동엽, 탁정애, 강헌중
서울대학교 지구환경과학부 해양천연물신약연구단,
The peroxisome proliferator-activated receptor δ (PPARδ) is a novel drug-target for metabolic disorders and identification of its ligands from natural sources and synthetic libraries will provide new opportunity to treat obesity and its associated diseases. We studied on PPARd to identify novel ligands for the nuclear receptor. A combination of natural product isolation, chemical modification and automated bioassay led to identification of several compounds as agonists with nano-molar affinities for the nuclear receptor PPARd. The ligands has >100,000-fold selectivity toward PPARd over the other subtypes, PPARa and PPARg. Treatment of mice with newly developed PPARd-selective agonists showed that the treated mice gained much less body weight than controls. As expected the treated mice showed reduced adiposity and improved glucose tolerance mainly due to fatty acid oxidation of lipid in peripheral tissues. Two hypercholesterolemic mouse models, apoE-/- and LDLR-/-, were treated with a newly developed PPARd-selective agonist. The ligand suppressed atherosclerotic lesion progression and reduced advanced atherosclerotic lesions in aorta. The underlying mechanism of ligand action will be discussed in detail.

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