Cargando…

Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway

Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and ami...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Yunxia, Dong, Weibing, Shao, Jing, Wang, Yibin, Zhou, Meiyi, Sun, Haipeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661165/
https://www.ncbi.nlm.nih.gov/pubmed/29118722
http://dx.doi.org/10.3389/fphys.2017.00853
_version_ 1783274432664436736
author Liu, Yunxia
Dong, Weibing
Shao, Jing
Wang, Yibin
Zhou, Meiyi
Sun, Haipeng
author_facet Liu, Yunxia
Dong, Weibing
Shao, Jing
Wang, Yibin
Zhou, Meiyi
Sun, Haipeng
author_sort Liu, Yunxia
collection PubMed
description Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation.
format Online
Article
Text
id pubmed-5661165
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-56611652017-11-08 Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway Liu, Yunxia Dong, Weibing Shao, Jing Wang, Yibin Zhou, Meiyi Sun, Haipeng Front Physiol Physiology Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA.Interestingly, BCAA starvation induced PI3K-AKT signaling. KLF15 induction by BCAA starvation was blocked by PI3K and AKT inhibitors, indicating the activation of PI3K-AKT signaling pathway mediated the KLF15 induction. BCAA regulated KLF15 expression at transcriptional level but not post-transcriptional level. However, BCAA starvation failed to increase the KLF15-promoter-driven luciferase expression, suggesting KLF15 promoter activity was not directly controlled by BCAA. Finally, fasting reduced BCAA abundance in mice and KLF15 expression was dramatically induced in muscle and white adipose tissue, but not in liver. Together, these data demonstrated BCAA negatively regulated KLF15 expression, suggesting a novel molecular mechanism underlying BCAA's multiple functions in metabolic regulation. Frontiers Media S.A. 2017-10-25 /pmc/articles/PMC5661165/ /pubmed/29118722 http://dx.doi.org/10.3389/fphys.2017.00853 Text en Copyright © 2017 Liu, Dong, Shao, Wang, Zhou and Sun. 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) or licensor 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 Physiology
Liu, Yunxia
Dong, Weibing
Shao, Jing
Wang, Yibin
Zhou, Meiyi
Sun, Haipeng
Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway
title Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway
title_full Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway
title_fullStr Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway
title_full_unstemmed Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway
title_short Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway
title_sort branched-chain amino acid negatively regulates klf15 expression via pi3k-akt pathway
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661165/
https://www.ncbi.nlm.nih.gov/pubmed/29118722
http://dx.doi.org/10.3389/fphys.2017.00853
work_keys_str_mv AT liuyunxia branchedchainaminoacidnegativelyregulatesklf15expressionviapi3kaktpathway
AT dongweibing branchedchainaminoacidnegativelyregulatesklf15expressionviapi3kaktpathway
AT shaojing branchedchainaminoacidnegativelyregulatesklf15expressionviapi3kaktpathway
AT wangyibin branchedchainaminoacidnegativelyregulatesklf15expressionviapi3kaktpathway
AT zhoumeiyi branchedchainaminoacidnegativelyregulatesklf15expressionviapi3kaktpathway
AT sunhaipeng branchedchainaminoacidnegativelyregulatesklf15expressionviapi3kaktpathway