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...
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| Format: | Article |
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Frontiers Media S.A.
2017-10-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphys.2017.00853/full |
| _version_ | 1818305608551497728 |
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| author | Yunxia Liu Weibing Dong Jing Shao Yibin Wang Meiyi Zhou Haipeng Sun |
| author_facet | Yunxia Liu Weibing Dong Jing Shao Yibin Wang Meiyi Zhou Haipeng Sun |
| author_sort | Yunxia Liu |
| collection | DOAJ |
| 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. |
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| id | doaj.art-45d14e7f171d497183d8dc1a51074ec4 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-13T06:29:18Z |
| publishDate | 2017-10-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj.art-45d14e7f171d497183d8dc1a51074ec42022-12-21T23:56:40ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2017-10-01810.3389/fphys.2017.00853307486Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT PathwayYunxia LiuWeibing DongJing ShaoYibin WangMeiyi ZhouHaipeng SunRecent 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.http://journal.frontiersin.org/article/10.3389/fphys.2017.00853/fullBCAAKlf15PI3KAktregulation |
| spellingShingle | Yunxia Liu Weibing Dong Jing Shao Yibin Wang Meiyi Zhou Haipeng Sun Branched-Chain Amino Acid Negatively Regulates KLF15 Expression via PI3K-AKT Pathway Frontiers in Physiology BCAA Klf15 PI3K Akt regulation |
| 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 | BCAA Klf15 PI3K Akt regulation |
| url | http://journal.frontiersin.org/article/10.3389/fphys.2017.00853/full |
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