Cargando…

Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism

Vascular protein sorting-associated protein 33B (VPS33B) plays important roles in hepatic polarity, which directly maintains the functional structure of the liver. It has reported that VPS33B has close association with arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Unfortunately,...

Descripción completa

Detalles Bibliográficos
Autores principales: Fu, Kaili, Wang, Conghui, Gao, Yue, Fan, Shicheng, Zhang, Huizhen, Sun, Jiahong, Jiang, Yiming, Liu, Conghui, Guan, Lihuan, Liu, Junling, Huang, Min, Bi, Huichang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439481/
https://www.ncbi.nlm.nih.gov/pubmed/30967781
http://dx.doi.org/10.3389/fphar.2019.00276
_version_ 1783407272014118912
author Fu, Kaili
Wang, Conghui
Gao, Yue
Fan, Shicheng
Zhang, Huizhen
Sun, Jiahong
Jiang, Yiming
Liu, Conghui
Guan, Lihuan
Liu, Junling
Huang, Min
Bi, Huichang
author_facet Fu, Kaili
Wang, Conghui
Gao, Yue
Fan, Shicheng
Zhang, Huizhen
Sun, Jiahong
Jiang, Yiming
Liu, Conghui
Guan, Lihuan
Liu, Junling
Huang, Min
Bi, Huichang
author_sort Fu, Kaili
collection PubMed
description Vascular protein sorting-associated protein 33B (VPS33B) plays important roles in hepatic polarity, which directly maintains the functional structure of the liver. It has reported that VPS33B has close association with arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Unfortunately, no further studies were conducted to reveal the role of Vps33b in the homeostasis of bile acids. In the current study, hepatic Vps33b-depleted male mice were used to investigate the metabolomics and lipidomics profiles of hepatic Vps33b deficiency based on ultrahigh-performance liquid chromatography coupled with an electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS) system. Hepatic Vps33b-depleted male mice displayed cholestasis and slight liver damage with increased serum levels of ALT, AST, ALP and T-Bili compared to wild-type mice. Targeted metabolomics analysis of bile acids revealed that increased taurine-conjugated bile acids accumulated in the serum of hepatic Vps33b-depleted mice, while unconjugated bile acids were prone to decrease, accompanied by the regulation of bile acid homeostasis-related genes. In addition, lipid profiles were significantly altered with the lack of Vps33b in the liver. A variety of lipids, such as triglycerides and sphingomyelins, were significantly decreased in the liver and increased in the serum of hepatic Vps33b-depleted mice compared to those in wild-type mice. Our study demonstrated that Vps33b influences the progress of liver metabolism both in bile acid circulation and lipid metabolism, which is involved in the progression of liver cholestasis in mice.
format Online
Article
Text
id pubmed-6439481
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-64394812019-04-09 Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism Fu, Kaili Wang, Conghui Gao, Yue Fan, Shicheng Zhang, Huizhen Sun, Jiahong Jiang, Yiming Liu, Conghui Guan, Lihuan Liu, Junling Huang, Min Bi, Huichang Front Pharmacol Pharmacology Vascular protein sorting-associated protein 33B (VPS33B) plays important roles in hepatic polarity, which directly maintains the functional structure of the liver. It has reported that VPS33B has close association with arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Unfortunately, no further studies were conducted to reveal the role of Vps33b in the homeostasis of bile acids. In the current study, hepatic Vps33b-depleted male mice were used to investigate the metabolomics and lipidomics profiles of hepatic Vps33b deficiency based on ultrahigh-performance liquid chromatography coupled with an electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS) system. Hepatic Vps33b-depleted male mice displayed cholestasis and slight liver damage with increased serum levels of ALT, AST, ALP and T-Bili compared to wild-type mice. Targeted metabolomics analysis of bile acids revealed that increased taurine-conjugated bile acids accumulated in the serum of hepatic Vps33b-depleted mice, while unconjugated bile acids were prone to decrease, accompanied by the regulation of bile acid homeostasis-related genes. In addition, lipid profiles were significantly altered with the lack of Vps33b in the liver. A variety of lipids, such as triglycerides and sphingomyelins, were significantly decreased in the liver and increased in the serum of hepatic Vps33b-depleted mice compared to those in wild-type mice. Our study demonstrated that Vps33b influences the progress of liver metabolism both in bile acid circulation and lipid metabolism, which is involved in the progression of liver cholestasis in mice. Frontiers Media S.A. 2019-03-22 /pmc/articles/PMC6439481/ /pubmed/30967781 http://dx.doi.org/10.3389/fphar.2019.00276 Text en Copyright © 2019 Fu, Wang, Gao, Fan, Zhang, Sun, Jiang, Liu, Guan, Liu, Huang and Bi. http://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 Pharmacology
Fu, Kaili
Wang, Conghui
Gao, Yue
Fan, Shicheng
Zhang, Huizhen
Sun, Jiahong
Jiang, Yiming
Liu, Conghui
Guan, Lihuan
Liu, Junling
Huang, Min
Bi, Huichang
Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism
title Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism
title_full Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism
title_fullStr Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism
title_full_unstemmed Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism
title_short Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism
title_sort metabolomics and lipidomics reveal the effect of hepatic vps33b deficiency on bile acids and lipids metabolism
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439481/
https://www.ncbi.nlm.nih.gov/pubmed/30967781
http://dx.doi.org/10.3389/fphar.2019.00276
work_keys_str_mv AT fukaili metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT wangconghui metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT gaoyue metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT fanshicheng metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT zhanghuizhen metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT sunjiahong metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT jiangyiming metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT liuconghui metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT guanlihuan metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT liujunling metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT huangmin metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism
AT bihuichang metabolomicsandlipidomicsrevealtheeffectofhepaticvps33bdeficiencyonbileacidsandlipidsmetabolism