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Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver
Hepatosteatosis, characterized by excessive accumulation of lipids in the liver, is a major health issue in modern society. Understanding how altered hepatic lipid metabolism/homeostasis causes hepatosteatosis helps to develop therapeutic interventions. Previous studies identify mitochondrial dysfun...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965806/ https://www.ncbi.nlm.nih.gov/pubmed/35372326 http://dx.doi.org/10.3389/fcell.2022.808140 |
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author | Du, Chongyangzi Yang, Wanchun Yu, Zongyan Yuan, Qiuyun Pang, Dejiang Tang, Ping Jiang, Wanxiang Chen, Mina Xiao, Bo |
author_facet | Du, Chongyangzi Yang, Wanchun Yu, Zongyan Yuan, Qiuyun Pang, Dejiang Tang, Ping Jiang, Wanxiang Chen, Mina Xiao, Bo |
author_sort | Du, Chongyangzi |
collection | PubMed |
description | Hepatosteatosis, characterized by excessive accumulation of lipids in the liver, is a major health issue in modern society. Understanding how altered hepatic lipid metabolism/homeostasis causes hepatosteatosis helps to develop therapeutic interventions. Previous studies identify mitochondrial dysfunction as a contributor to hepatosteatosis. But, the molecular mechanisms of mitochondrial dysfunction leading to altered lipid metabolism remain incompletely understood. Our previous work shows that Rheb, a Ras-like small GTPase, not only activates mTORC1 but also promotes mitochondrial ATP production through pyruvate dehydrogenase (PDH). In this study, we further demonstrate that Rheb controls hepatic triglyceride secretion and reduces diet-induced lipid accumulation in a mouse liver. Genetic deletion of Rheb causes rapid and spontaneous steatosis in the liver, which is unexpected from the role of mTORC1 that enhances lipid synthesis, whereas Rheb transgene remarkably reduces diet-induced hepatosteatosis. Results suggest that the hepatosteatosis in Rheb KO is an outcome of impaired lipid secretion, which is linked to mitochondrial ATP production of hepatocytes. Our findings highlight an under-appreciated role of Rheb in the regulation of hepatic lipid secretion through mitochondrial energy production, with therapeutic implication. |
format | Online Article Text |
id | pubmed-8965806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89658062022-03-31 Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver Du, Chongyangzi Yang, Wanchun Yu, Zongyan Yuan, Qiuyun Pang, Dejiang Tang, Ping Jiang, Wanxiang Chen, Mina Xiao, Bo Front Cell Dev Biol Cell and Developmental Biology Hepatosteatosis, characterized by excessive accumulation of lipids in the liver, is a major health issue in modern society. Understanding how altered hepatic lipid metabolism/homeostasis causes hepatosteatosis helps to develop therapeutic interventions. Previous studies identify mitochondrial dysfunction as a contributor to hepatosteatosis. But, the molecular mechanisms of mitochondrial dysfunction leading to altered lipid metabolism remain incompletely understood. Our previous work shows that Rheb, a Ras-like small GTPase, not only activates mTORC1 but also promotes mitochondrial ATP production through pyruvate dehydrogenase (PDH). In this study, we further demonstrate that Rheb controls hepatic triglyceride secretion and reduces diet-induced lipid accumulation in a mouse liver. Genetic deletion of Rheb causes rapid and spontaneous steatosis in the liver, which is unexpected from the role of mTORC1 that enhances lipid synthesis, whereas Rheb transgene remarkably reduces diet-induced hepatosteatosis. Results suggest that the hepatosteatosis in Rheb KO is an outcome of impaired lipid secretion, which is linked to mitochondrial ATP production of hepatocytes. Our findings highlight an under-appreciated role of Rheb in the regulation of hepatic lipid secretion through mitochondrial energy production, with therapeutic implication. Frontiers Media S.A. 2022-03-16 /pmc/articles/PMC8965806/ /pubmed/35372326 http://dx.doi.org/10.3389/fcell.2022.808140 Text en Copyright © 2022 Du, Yang, Yu, Yuan, Pang, Tang, Jiang, Chen and Xiao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Du, Chongyangzi Yang, Wanchun Yu, Zongyan Yuan, Qiuyun Pang, Dejiang Tang, Ping Jiang, Wanxiang Chen, Mina Xiao, Bo Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver |
title | Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver |
title_full | Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver |
title_fullStr | Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver |
title_full_unstemmed | Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver |
title_short | Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver |
title_sort | rheb promotes triglyceride secretion and ameliorates diet-induced steatosis in the liver |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8965806/ https://www.ncbi.nlm.nih.gov/pubmed/35372326 http://dx.doi.org/10.3389/fcell.2022.808140 |
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