OPA1 affects lipid metabolism and atherosclerosis progression

脂质代谢 新陈代谢 医学 内科学 内分泌学 生物 心脏病学
作者
Lorenzo Da Dalt,Annalisa Moregola,M Svecla,Silvia Pedretti,F Fantini,Elena Donetti,Nico Mitro,Luca Scorrano,Giuseppe Danilo Norata
出处
期刊:Cardiovascular Research [Oxford University Press]
卷期号:120 (Supplement_1)
标识
DOI:10.1093/cvr/cvae088.151
摘要

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): European Atherosclerosis Society Introduction Mitochondria are involved in cellular metabolism, energy generation, calcium homeostasis, sterol and bile acids (BAs) production. Mitochondria continuously undergo biogenesis, fusion, fission and mitophagy, maintaining a continuous balance between all forms. Purpose On these premises, we test the impact of OPA1, an inner mitochondria membrane fusion protein, on mitochondrial tethering on lipid metabolism in the liver and the atherosclerotic plaque. Methods OPA1HepKO and OPA1 TG on LDLR KO background were fed with a Western-type diet (WTD) respectively for 12 weeks. Inverse calorimetry, GTT, and LipidToleranceTest (LTT) were performed. Paraffin-embedded tissues were used for histological analysis, frozen tissues were used for OMICs analysis. VSMCs were isolated and cultured with VLDL (50 µg/ml). Results While OPA1HepKO mice display altered systemic metabolism with reduced body weight and reduced circulating lipid levels OPA1 overexpression on LDLR KO background showed significantly high cholesterol levels. OPA1 deficiency impair hepatic bile acid conjugation with significant accumulation of primary unconjugated bile acids in the liver. On the contrary OPA1 overexpression leads to a reduction of unconjugated bile acids and higher percentage of conjugated bile acids. OPA1 reduction leads to a reduced atherosclerotic plaque while, on the contrary, its overexpression doesn’t affect atherosclerosis despite an increase in circulating lipid and lipoprotein levels. OPA1 overexpression is therefore promoting plaque stabilization with VSMCs that are less prone to change their metabolism to synthetic. Conclusion Hepatic Opa1 deficiency alters bile acids production and therefore circulating lipid profile with a consequent reduction in atherosclerotic plaque formation. OPA1 overexpression in the aorta affects plaque stability despite the highest levels of circulating lipids.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Cloud完成签到 ,获得积分10
刚刚
影子发布了新的文献求助10
2秒前
3秒前
王子安应助科研通管家采纳,获得10
3秒前
猪猪hero应助科研通管家采纳,获得10
3秒前
研友_VZG7GZ应助科研通管家采纳,获得10
3秒前
所所应助科研通管家采纳,获得10
3秒前
王子安应助科研通管家采纳,获得10
3秒前
3秒前
云染完成签到 ,获得积分10
4秒前
roy发布了新的文献求助10
5秒前
酷波er应助yiryir采纳,获得10
5秒前
李爱国应助善木兰采纳,获得10
7秒前
7秒前
梅子发布了新的文献求助10
7秒前
权思远发布了新的文献求助10
8秒前
牛文文发布了新的文献求助10
12秒前
12秒前
权思远完成签到,获得积分10
13秒前
梅子完成签到,获得积分10
14秒前
15秒前
英姑应助上好佳采纳,获得10
16秒前
温婉的香氛完成签到 ,获得积分10
17秒前
yiryir发布了新的文献求助10
17秒前
林林发布了新的文献求助10
18秒前
善学以致用应助红领巾klj采纳,获得10
18秒前
俭朴新之完成签到 ,获得积分10
19秒前
qyn1234566发布了新的文献求助20
20秒前
20秒前
封闭货车完成签到,获得积分10
21秒前
Alicyclobacillus完成签到,获得积分10
21秒前
善木兰发布了新的文献求助10
23秒前
24秒前
25秒前
28秒前
上好佳发布了新的文献求助10
28秒前
愉快西牛完成签到,获得积分10
28秒前
起风了完成签到,获得积分10
29秒前
xuzj应助qyn1234566采纳,获得10
30秒前
量子星尘发布了新的文献求助10
31秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988997
求助须知:如何正确求助?哪些是违规求助? 3531351
关于积分的说明 11253520
捐赠科研通 3269928
什么是DOI,文献DOI怎么找? 1804830
邀请新用户注册赠送积分活动 882063
科研通“疑难数据库(出版商)”最低求助积分说明 809068