Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt Pathway
The liver circadian clock plays a pivotal role in driving metabolic rhythms, being primarily entrained by the feeding schedule, although the underlying mechanisms remain elusive. This study aimed to investigate the potential role of insulin as an intake signal mediating liver entrainment in fish. To...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/15/11897 |
| _version_ | 1797586745261293568 |
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| author | Nuria Saiz Cristina Velasco Nuria de Pedro José Luis Soengas Esther Isorna |
| author_facet | Nuria Saiz Cristina Velasco Nuria de Pedro José Luis Soengas Esther Isorna |
| author_sort | Nuria Saiz |
| collection | DOAJ |
| description | The liver circadian clock plays a pivotal role in driving metabolic rhythms, being primarily entrained by the feeding schedule, although the underlying mechanisms remain elusive. This study aimed to investigate the potential role of insulin as an intake signal mediating liver entrainment in fish. To achieve this, the expression of clock genes, which form the molecular basis of endogenous oscillators, was analyzed in goldfish liver explants treated with insulin. The presence of insulin directly increased the abundance of <i>per1a</i> and <i>per2</i> transcripts in the liver. The dependency of protein translation for such insulin effects was evaluated using cycloheximide, which revealed that intermediate protein translation is seemingly unnecessary for the observed insulin actions. Furthermore, the putative interaction between insulin and glucocorticoid signaling in the liver was examined, with the results suggesting that both hormones exert their effects by independent mechanisms. Finally, to investigate the specific pathways involved in the insulin effects, inhibitors targeting PI3K/AKT and MEK/ERK were employed. Notably, inhibition of PI3K/AKT pathway prevented the induction of <i>per</i> genes by insulin, supporting its involvement in this process. Together, these findings suggest a role of insulin in fish as a key element of the multifactorial system that entrains the liver clock to the feeding schedule. |
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| id | doaj.art-82ebaec95f1c44e0840b05a9efe6e64c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:26:34Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-82ebaec95f1c44e0840b05a9efe6e64c2023-11-18T22:57:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151189710.3390/ijms241511897Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt PathwayNuria Saiz0Cristina Velasco1Nuria de Pedro2José Luis Soengas3Esther Isorna4Department of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, SpainCentro de Investigación Mariña, Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Universidade de Vigo, 36310 Vigo, SpainDepartment of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, SpainCentro de Investigación Mariña, Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Universidade de Vigo, 36310 Vigo, SpainDepartment of Genetics, Physiology and Microbiology, Faculty of Biological Sciences, Complutense University of Madrid, 28040 Madrid, SpainThe liver circadian clock plays a pivotal role in driving metabolic rhythms, being primarily entrained by the feeding schedule, although the underlying mechanisms remain elusive. This study aimed to investigate the potential role of insulin as an intake signal mediating liver entrainment in fish. To achieve this, the expression of clock genes, which form the molecular basis of endogenous oscillators, was analyzed in goldfish liver explants treated with insulin. The presence of insulin directly increased the abundance of <i>per1a</i> and <i>per2</i> transcripts in the liver. The dependency of protein translation for such insulin effects was evaluated using cycloheximide, which revealed that intermediate protein translation is seemingly unnecessary for the observed insulin actions. Furthermore, the putative interaction between insulin and glucocorticoid signaling in the liver was examined, with the results suggesting that both hormones exert their effects by independent mechanisms. Finally, to investigate the specific pathways involved in the insulin effects, inhibitors targeting PI3K/AKT and MEK/ERK were employed. Notably, inhibition of PI3K/AKT pathway prevented the induction of <i>per</i> genes by insulin, supporting its involvement in this process. Together, these findings suggest a role of insulin in fish as a key element of the multifactorial system that entrains the liver clock to the feeding schedule.https://www.mdpi.com/1422-0067/24/15/11897circadian systemfood-entrainable oscillator (FEO)<i>Carassius auratus</i>insulinliverperiod genes |
| spellingShingle | Nuria Saiz Cristina Velasco Nuria de Pedro José Luis Soengas Esther Isorna Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt Pathway International Journal of Molecular Sciences circadian system food-entrainable oscillator (FEO) <i>Carassius auratus</i> insulin liver period genes |
| title | Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt Pathway |
| title_full | Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt Pathway |
| title_fullStr | Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt Pathway |
| title_full_unstemmed | Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt Pathway |
| title_short | Insulin Controls Clock Gene Expression in the Liver of Goldfish Probably via Pi3k/Akt Pathway |
| title_sort | insulin controls clock gene expression in the liver of goldfish probably via pi3k akt pathway |
| topic | circadian system food-entrainable oscillator (FEO) <i>Carassius auratus</i> insulin liver period genes |
| url | https://www.mdpi.com/1422-0067/24/15/11897 |
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