间歇性禁食如何改变肝酶并帮助预防疾病 How intermittent fasting changes liver enzymes and helps prevent disease

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News Release 10-Mar-2020

Research on mice reveals surprising impact on fat metabolism

University of Sydney

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IMAGE: Dr Mark Larance from the Charles Perkins Centre and School of Life and Environmental Sciences at the University of Sydney. view more  Credit: Stefanie Zingsheim/University of Sydney

Researchers in Australia have used state-of-the-art analytical tools to understand how intermittent fasting works on the liver to help prevent disease. The findings will help medical scientists working in cancer, cardiovascular and diabetes research develop new interventions to lower disease risk and discover the optimum intervals for fasting.

In experiments with mice, researchers led by Dr Mark Larance at the University of Sydney identified how every-other-day fasting affected proteins in the liver, showing unexpected impact on fatty acid metabolism and the surprising role played by a master regulator protein that controls many biological pathways in the liver and other organs.

“We know that fasting can be an effective intervention to treat disease and improve liver health. But we haven’t known how fasting reprograms liver proteins, which perform a diverse array of essential metabolic functions,” said Dr Larance, a Cancer Institute of NSW Future Research Fellow in the Charles Perkins Centre and School of Life and Environmental Sciences at the University of Sydney.

“By studying the impact on proteins in the livers of mice, which are suitable human biological models, we now have a much better understanding of how this happens.”

In particular, the researchers found that the HNF4-(alpha) protein, which regulates a large number of liver genes, plays a previously unknown role during intermittent fasting.

“For the first time we showed that HNF4-(alpha) is inhibited during intermittent fasting. This has downstream consequences, such as lowering the abundance of blood proteins in inflammation or affecting bile synthesis. This helps explain some of the previously known facts about intermittent fasting,” Dr Larance said.

The researchers also found that every-other-day-fasting – where no food was consumed on alternate days – changed the metabolism of fatty acids in the liver, knowledge that could be applied to improvements in glucose tolerance and the regulation of diabetes.

“What’s really exciting is that this new knowledge about the role of HNF4-(alpha) means it could be possible to mimic some of the effects of intermittent fasting through the development of liver-specific HNF4-(alpha) regulators,” Dr Larance said.

The research, published today in Cell Reports, was done in collaboration with the Heart Research Institute and Dr John O’Sullivan at Royal Prince Alfred Hospital. Dr O’Sullivan is an Adjunct Professor in the Faculty of Medicine & Health and a Senior Lecturer at the Sydney Medical School.

A technique known as multi-Omics, which considers multiple data sets such as the total collection of proteins and genes, was used in the study, allowing for the integration of large amounts of information to discover new associations within biological systems.

Dr O’Sullivan said: “These multi-Omics approaches give us unprecedented insight into biological systems. We are able to build very sophisticated models by bringing together all the moving parts.”

The multi-Omics data was obtained at Sydney Mass Spectrometry, part of the University of Sydney’s Core Research Facilities.

Dr Larance said that the information can now be used in future studies to determine optimum fasting periods to regulate protein response in the liver.

“Last year we published research into the impact of every-other-day-fasting on humans. Using these mouse data, we can now build up improved models of fasting for better human health.”

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DOWNLOAD photos of Dr Mark Larance at this link.

INTERVIEWS

Dr Mark Larance | [email protected]
Charles Perkins Centre and School of Life and Environmental Sciences
The University of Sydney, Australia

MEDIA ENQUIRIES

Marcus Strom | +61 423 982 485 | [email protected]

DECLARATION

This research was supported by grants from the National Health and Medical Research Council (APP1120475). Dr Mark Larance is a Cancer Institute NSW Future Research Leader Fellow. Dr John O’Sullivan is supported by a Sydney Medical School Chapman Fellowship, by the Heart Research Institute and a NSW Department of Health Clinician-Scientist Award (DOH1006). Yen Chin Koay is supported by the Heart Research Institute.

澳大利亚的研究人员已使用最先进的分析工具来了解间歇性禁食如何在肝脏上起作用以帮助预防疾病。这些发现将帮助从事癌症,心血管和糖尿病研究的医学科学家开发新的干预措施,以降低疾病风险并发现禁食的最佳间隔。

在老鼠的实验中,悉尼大学马克·拉兰斯博士领导的研究人员确定了每天禁食如何影响肝脏中的蛋白质,显示出对脂肪酸代谢的意外影响以及控制许多人的主调节蛋白发挥的惊人作用肝脏和其他器官中的生物途径。

“我们知道,禁食可以有效治疗疾病并改善肝脏健康。但是我们还不知道禁食如何重编程能执行多种基本代谢功能的肝蛋白,”新南威尔士州癌症研究学院查尔斯·珀金斯中心和大学生命与环境科学学院的研究员拉兰斯博士说。悉尼

“通过研究对小鼠肝脏蛋白质的影响(这是合适的人类生物学模型),我们现在对这是如何发生的有了更好的了解。”

研究人员尤其发现,调节大量肝脏基因的HNF4-α蛋白在间歇性禁食中起着以前未知的作用。

“我们首次证明在间歇性禁食期间HNF4-α被抑制。这具有下游后果,例如降低炎症中的血液蛋白丰度或影响胆汁合成。这有助于解释一些有关间歇性禁食的先前已知事实。”

研究人员还发现,每隔一天禁食-隔天不吃任何食物-改变了肝脏中脂肪酸的代谢,这一知识可用于改善葡萄糖耐量和糖尿病的控制。

Larance博士说:“真正令人兴奋的是,有关HNF4-α的新知识意味着有可能通过开发肝特异性HNF4-α调节剂来模拟间歇性禁食的某些影响。” 。

这项研究今天发表在《细胞报告》上,是与心脏研究所和皇家阿尔弗雷德王子医院的约翰·奥沙利文博士合作完成的。 O’Sullivan博士是医学与卫生学院的兼职教授,也是悉尼医学院的高级讲师。

在这项研究中使用了一种被称为多组学的技术,该技术考虑了多个数据集,例如蛋白质和基因的总收集量,从而允许整合大量信息以发现生物系统内的新关联。

奥沙利文博士说:“这些多组学方法使我们对生物系统有了空前的见识。通过整合所有运动部件,我们能够构建非常复杂的模型。”

多组化合物的数据是从悉尼大学核心研究机构悉尼质谱仪获得的。

拉兰斯博士说,这些信息现在可以用于将来的研究中,以确定调节肝脏中蛋白质反应的最佳禁食期。

“去年,我们发表了禁食对人类的影响的研究。使用这些鼠标数据,我们现在可以建立改进的禁食模型,以改善人体健康。”

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