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Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle

SIMPLE SUMMARY: Myostatin (MSTN) gene knockout can increase lean muscle mass and has been widely used in livestock breeding. MSTN deficiency also regulates various metabolic processes. However, the effect of MSTN knockout on the liver, the largest metabolic organ, has not been reported. In this stud...

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Autores principales: Wu, Di, Gu, Mingjuan, Wei, Zhuying, Bai, Chunling, Su, Guanghua, Liu, Xuefei, Zhao, Yuefang, Yang, Lei, Li, Guangpeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772948/
https://www.ncbi.nlm.nih.gov/pubmed/35049827
http://dx.doi.org/10.3390/ani12020205
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author Wu, Di
Gu, Mingjuan
Wei, Zhuying
Bai, Chunling
Su, Guanghua
Liu, Xuefei
Zhao, Yuefang
Yang, Lei
Li, Guangpeng
author_facet Wu, Di
Gu, Mingjuan
Wei, Zhuying
Bai, Chunling
Su, Guanghua
Liu, Xuefei
Zhao, Yuefang
Yang, Lei
Li, Guangpeng
author_sort Wu, Di
collection PubMed
description SIMPLE SUMMARY: Myostatin (MSTN) gene knockout can increase lean muscle mass and has been widely used in livestock breeding. MSTN deficiency also regulates various metabolic processes. However, the effect of MSTN knockout on the liver, the largest metabolic organ, has not been reported. In this study, physiological and biochemical parameters of serum, untargeted and targeted metabolomics of MSTN(+/−) and WT cattle were studied, and we found that the knockout of MSTN could regulate liver metabolism and promote bile acid metabolism. This may be due to the enhanced expression of bile acid synthesis genes in MSTN(+/−) bovine livers. In conclusion, MSTN knockout regulated bile acid metabolism via enhanced bile acid synthesis. ABSTRACT: Myostatin (MSTN) is a major negative regulator of skeletal muscle mass and causes a variety of metabolic changes. However, the effect of MSTN knockout on bile acid metabolism has rarely been reported. In this study, the physiological and biochemical alterations of serum in MSTN(+/−) and wild type (WT) cattle were investigated. There were no significant changes in liver and kidney biochemical indexes. However, compared with the WT cattle, lactate dehydrogenase, total bile acid (TBA), cholesterol, and high-density lipoprotein (HDL) in the MSTN(+/−) cattle were significantly increased, and glucose, low-density lipoprotein (LDL), and triglycerides (TG) were significantly decreased, indicating that MSTN knockout affected glucose and lipid metabolism and total bile acids content. Targeted metabolomic analysis of the bile acids and their derivatives was performed on serum samples and found that bile acids were significantly increased in the MSTN(+/−) cattle compared with the WT cattle. As the only bile acid synthesis organ in the body, we performed metabolomic analysis on the liver to study the effect of MSTN knockout on hepatic metabolism. Metabolic pathway enrichment analysis of differential metabolites showed significant enrichment of the primary bile acid biosynthesis and bile secretion pathway in the MSTN(+/−) cattle. Targeted metabolomics data further showed that MSTN knockout significantly increased bile acid content in the liver, which may have resulted from enhanced bile acid synthesis due to the expression of bile acid synthesis genes, cholesterol 7 alpha-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1), and upregulation in the liver of the MSTN(+/−) cattle. These results indicate that MSTN knockout does not adversely affect bovine fitness but regulates bile acid metabolism via enhanced bile acid synthesis. This further suggests a role of MSTN in regulating metabolism.
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spelling pubmed-87729482022-01-21 Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle Wu, Di Gu, Mingjuan Wei, Zhuying Bai, Chunling Su, Guanghua Liu, Xuefei Zhao, Yuefang Yang, Lei Li, Guangpeng Animals (Basel) Article SIMPLE SUMMARY: Myostatin (MSTN) gene knockout can increase lean muscle mass and has been widely used in livestock breeding. MSTN deficiency also regulates various metabolic processes. However, the effect of MSTN knockout on the liver, the largest metabolic organ, has not been reported. In this study, physiological and biochemical parameters of serum, untargeted and targeted metabolomics of MSTN(+/−) and WT cattle were studied, and we found that the knockout of MSTN could regulate liver metabolism and promote bile acid metabolism. This may be due to the enhanced expression of bile acid synthesis genes in MSTN(+/−) bovine livers. In conclusion, MSTN knockout regulated bile acid metabolism via enhanced bile acid synthesis. ABSTRACT: Myostatin (MSTN) is a major negative regulator of skeletal muscle mass and causes a variety of metabolic changes. However, the effect of MSTN knockout on bile acid metabolism has rarely been reported. In this study, the physiological and biochemical alterations of serum in MSTN(+/−) and wild type (WT) cattle were investigated. There were no significant changes in liver and kidney biochemical indexes. However, compared with the WT cattle, lactate dehydrogenase, total bile acid (TBA), cholesterol, and high-density lipoprotein (HDL) in the MSTN(+/−) cattle were significantly increased, and glucose, low-density lipoprotein (LDL), and triglycerides (TG) were significantly decreased, indicating that MSTN knockout affected glucose and lipid metabolism and total bile acids content. Targeted metabolomic analysis of the bile acids and their derivatives was performed on serum samples and found that bile acids were significantly increased in the MSTN(+/−) cattle compared with the WT cattle. As the only bile acid synthesis organ in the body, we performed metabolomic analysis on the liver to study the effect of MSTN knockout on hepatic metabolism. Metabolic pathway enrichment analysis of differential metabolites showed significant enrichment of the primary bile acid biosynthesis and bile secretion pathway in the MSTN(+/−) cattle. Targeted metabolomics data further showed that MSTN knockout significantly increased bile acid content in the liver, which may have resulted from enhanced bile acid synthesis due to the expression of bile acid synthesis genes, cholesterol 7 alpha-hydroxylase (CYP7A1) and sterol 27-hydroxylase (CYP27A1), and upregulation in the liver of the MSTN(+/−) cattle. These results indicate that MSTN knockout does not adversely affect bovine fitness but regulates bile acid metabolism via enhanced bile acid synthesis. This further suggests a role of MSTN in regulating metabolism. MDPI 2022-01-15 /pmc/articles/PMC8772948/ /pubmed/35049827 http://dx.doi.org/10.3390/ani12020205 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wu, Di
Gu, Mingjuan
Wei, Zhuying
Bai, Chunling
Su, Guanghua
Liu, Xuefei
Zhao, Yuefang
Yang, Lei
Li, Guangpeng
Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle
title Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle
title_full Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle
title_fullStr Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle
title_full_unstemmed Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle
title_short Myostatin Knockout Regulates Bile Acid Metabolism by Promoting Bile Acid Synthesis in Cattle
title_sort myostatin knockout regulates bile acid metabolism by promoting bile acid synthesis in cattle
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772948/
https://www.ncbi.nlm.nih.gov/pubmed/35049827
http://dx.doi.org/10.3390/ani12020205
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