초록 ▼

o 식이유도 비만쥐에서의 TG1009의 효과는 위 ob/ob mouse에서의 결과와 비슷하였어나, TG1009의 투여량이 많이 요구되었었다. 이상과 같은 전임상 동물실험에서 IDPc target validation으로서의 TG1009는 일부 성공을 거두었다고 판단됨.
o IDPc 효소활성 저해 물질로 검색되어진 TG1044 와 TG10441 (TG1044 유도체)는 세포수준에서 세포비만화를 저해하였으며 그 작용기작을 밝혔음.
o TG1044의 경우 세포지방화의 저해능은 TG1009와 약간 다른 양상으로 나타났는데, TG1

o 식이유도 비만쥐에서의 TG1009의 효과는 위 ob/ob mouse에서의 결과와 비슷하였어나, TG1009의 투여량이 많이 요구되었었다. 이상과 같은 전임상 동물실험에서 IDPc target validation으로서의 TG1009는 일부 성공을 거두었다고 판단됨.
o IDPc 효소활성 저해 물질로 검색되어진 TG1044 와 TG10441 (TG1044 유도체)는 세포수준에서 세포비만화를 저해하였으며 그 작용기작을 밝혔음.
o TG1044의 경우 세포지방화의 저해능은 TG1009와 약간 다른 양상으로 나타났는데, TG1009의 경우 adipogenesis 전 과정에서 (early, medial and late stage) 저해하였어나, TG1045의 경우 early stage에서만 세포 지방화를 저해하였다. 이러한 결과는 분자생물학적 adipogenic gene expression pattern과도 일치하였음.
o 제 2차년도 하반기에서 TG1044에 대한 비만동물모델에서 그 효능을 검정하였음.
o TG1022는 IDPc의 활성을 저해하며, AMPK의 활성을 올려주는 2중의 효능을 보이는 물질로서, in vitro, in vivo에서 adipogenesis를 저해하였으며, 체중을 줄여주었음.

Abstract ▼

We proposed to develop a new concept of nutraceutical with plant extract, which was effective on body weight reduction in animal tests. In our preliminary experiment, blocking an early stage of adipogenesis resulted in weight loss and reduction in total plasma lipid content in ob/ob mice. While we h

We proposed to develop a new concept of nutraceutical with plant extract, which was effective on body weight reduction in animal tests. In our preliminary experiment, blocking an early stage of adipogenesis resulted in weight loss and reduction in total plasma lipid content in ob/ob mice. While we have succeeded to reduce body weight with a chemical and a plant extract, which reduced the generation of NADPH, we needed to screen additional plant extracts having higher potency. It was our purpose to develop a nutraceutical for weight reduction and hyperlipidemia, but in long run to develop a medicine for the diseases is our ultimate goal.
NADPH is an essential co-factor for the syntheses of fatty acids and cholesterol. In our preliminary research, cytosolic isocitrate dehydrogenase (IDPc) is one of the NADPH suppliers in lipogenic tissues, liver and adipocytes. Nonetheless, the role of cytosolic $NADP^+$-dependent isocitrate dehydrogenase (IDPc) in lipid metabolic processes has not been well assessed. Since IDPc appears not to be coupled to other physiologically important metabolism, the enzyme could be the best target for reducing NADPH supply in those tissues over other well-known NADPH producers, glucose-6-phosphate dehydrogenase (G6PDH), 6-phospho-glucuronate dehydrogenase(PGDH) and malic enzyme.
When we treated IDPc inhibitors on 3T3-L1 cells, a predisposed adipogenic cell line, the adipogenesis of the cells were blocked nearly completely in a low dose. Treatment of IDPc inhibitors, as blockers for an early stage of adipogenesis in lipogenic tissues, have resulted in weight loss and reduction in total plasma lipid content in ob/ob mice as well as in diet-induced obese mice. Once we find materials with a higher potency of inhibiting IDPc but without toxicity, there would be a great chance to develope a novel way to reduce weight in obese people and cut down the fat levels in hyperlipidemia patients. Presently rigorous screening from various sources including plant extracts is underway.

목차 Contents

• 표지...1
• 제출문...2
• 보고서 초록...3
• 요약문....4
• SUMMARY...6
• CONTENTS...7목차...8제 1 장 연구개발과제의 개요...10
• 제 2 장 국내외 기술개발 현황...33
• 제 3 장 연구개발수행 내용 및 결과...35
• 제 4 장 목표달성도 및 관련분야에의 기여도...44
• 제 5 장 연구개발결과의 활용계획...49
• 제 6 장 연구개발과정에서 수집한 해외과학기술정보...50
• 제 7 장 참고문헌...53