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Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes

Liver has numerous critical metabolic functions including lipid metabolism, which is usually dysregulated in obesity, the metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates bone morphogenetic proteins (BMPs) play an important role in adipogenesis and the...

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Autores principales: Peng, Qi, Chen, Bin, Wang, Hao, Zhu, Ying, Wu, Jinghong, Luo, Yetao, Zuo, Guowei, Luo, Jinyong, Zhou, Lan, Shi, Qiong, Weng, Yaguang, Huang, Ailong, He, Tong-Chuan, Fan, Jiaming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932923/
https://www.ncbi.nlm.nih.gov/pubmed/31831718
http://dx.doi.org/10.18632/aging.102552
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author Peng, Qi
Chen, Bin
Wang, Hao
Zhu, Ying
Wu, Jinghong
Luo, Yetao
Zuo, Guowei
Luo, Jinyong
Zhou, Lan
Shi, Qiong
Weng, Yaguang
Huang, Ailong
He, Tong-Chuan
Fan, Jiaming
author_facet Peng, Qi
Chen, Bin
Wang, Hao
Zhu, Ying
Wu, Jinghong
Luo, Yetao
Zuo, Guowei
Luo, Jinyong
Zhou, Lan
Shi, Qiong
Weng, Yaguang
Huang, Ailong
He, Tong-Chuan
Fan, Jiaming
author_sort Peng, Qi
collection PubMed
description Liver has numerous critical metabolic functions including lipid metabolism, which is usually dysregulated in obesity, the metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates bone morphogenetic proteins (BMPs) play an important role in adipogenesis and thermogenic balance in adipogenic progenitors and adipose tissue. However, the direct impact of BMPs on hepatic steatosis and possible association with NAFLD are poorly understood. Here, we found that BMP4 was up-regulated in oleic acid-induced steatosis and during the development of high fat diet (HFD)-induced NAFLD. Exogenous BMP4 reduced lipid accumulation and up-regulated the genes involved in lipid synthesis, storage and breakdown in hepatocytes. Exogenous BMP4 inhibited hepatic steatosis, reduced serum triglyceride levels and body weight, and alleviated progression of NAFLD in vivo. Mechanistically, BMP4 overexpression in hepatocytes down-regulated most components of the mTORC1 signaling axis. Collectively, these findings strongly suggest that BMP4 may play an essential role in regulating hepatic lipid metabolism and the molecular pathogenesis of NAFLD. Manipulating BMP4 and/or mTORC1 signaling axis may lead to the development of novel therapeutics for obesity, metabolic syndrome, and NAFLD.
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spelling pubmed-69329232020-01-03 Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes Peng, Qi Chen, Bin Wang, Hao Zhu, Ying Wu, Jinghong Luo, Yetao Zuo, Guowei Luo, Jinyong Zhou, Lan Shi, Qiong Weng, Yaguang Huang, Ailong He, Tong-Chuan Fan, Jiaming Aging (Albany NY) Research Paper Liver has numerous critical metabolic functions including lipid metabolism, which is usually dysregulated in obesity, the metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates bone morphogenetic proteins (BMPs) play an important role in adipogenesis and thermogenic balance in adipogenic progenitors and adipose tissue. However, the direct impact of BMPs on hepatic steatosis and possible association with NAFLD are poorly understood. Here, we found that BMP4 was up-regulated in oleic acid-induced steatosis and during the development of high fat diet (HFD)-induced NAFLD. Exogenous BMP4 reduced lipid accumulation and up-regulated the genes involved in lipid synthesis, storage and breakdown in hepatocytes. Exogenous BMP4 inhibited hepatic steatosis, reduced serum triglyceride levels and body weight, and alleviated progression of NAFLD in vivo. Mechanistically, BMP4 overexpression in hepatocytes down-regulated most components of the mTORC1 signaling axis. Collectively, these findings strongly suggest that BMP4 may play an essential role in regulating hepatic lipid metabolism and the molecular pathogenesis of NAFLD. Manipulating BMP4 and/or mTORC1 signaling axis may lead to the development of novel therapeutics for obesity, metabolic syndrome, and NAFLD. Impact Journals 2019-12-12 /pmc/articles/PMC6932923/ /pubmed/31831718 http://dx.doi.org/10.18632/aging.102552 Text en Copyright © 2019 Peng et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Peng, Qi
Chen, Bin
Wang, Hao
Zhu, Ying
Wu, Jinghong
Luo, Yetao
Zuo, Guowei
Luo, Jinyong
Zhou, Lan
Shi, Qiong
Weng, Yaguang
Huang, Ailong
He, Tong-Chuan
Fan, Jiaming
Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes
title Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes
title_full Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes
title_fullStr Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes
title_full_unstemmed Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes
title_short Bone morphogenetic protein 4 (BMP4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mTORC1 signaling axis in hepatocytes
title_sort bone morphogenetic protein 4 (bmp4) alleviates hepatic steatosis by increasing hepatic lipid turnover and inhibiting the mtorc1 signaling axis in hepatocytes
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932923/
https://www.ncbi.nlm.nih.gov/pubmed/31831718
http://dx.doi.org/10.18632/aging.102552
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