Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish

Diabetes has gradually become a serious disease that threatens human health. It can induce various complications, and the pathogenesis of diabetes is quite complex and not yet fully elucidated. The zebrafish has been widely acknowledged as a useful model for investigating the mechanisms underlying t...

Full description

Bibliographic Details
Main Authors: Guodong Ge, Jing Ren, Guili Song, Qing Li, Zongbin Cui
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/15/11994
_version_ 1797586671498166272
author Guodong Ge
Jing Ren
Guili Song
Qing Li
Zongbin Cui
author_facet Guodong Ge
Jing Ren
Guili Song
Qing Li
Zongbin Cui
author_sort Guodong Ge
collection DOAJ
description Diabetes has gradually become a serious disease that threatens human health. It can induce various complications, and the pathogenesis of diabetes is quite complex and not yet fully elucidated. The zebrafish has been widely acknowledged as a useful model for investigating the mechanisms underlying the pathogenesis and therapeutic interventions of diabetes. However, the molecular basis of zebrafish diabetes induced by overfeeding remains unknown. In this study, a zebrafish diabetes model was established by overfeeding, and the molecular basis of zebrafish diabetes induced by overfeeding was explored. Compared with the control group, the body length, body weight, and condition factor index of zebrafish increased significantly after four weeks of overfeeding. There was a significant elevation in the fasting blood glucose level, accompanied by a large number of lipid droplets accumulated within the liver. The levels of triglycerides and cholesterol in both the serum and liver exhibited a statistically significant increase. Transcriptome sequencing was employed to investigate changes in the livers of overfed zebrafish. The number of up-regulated and down-regulated differentially expressed genes (DEGs) was 1582 and 2404, respectively, in the livers of overfed zebrafish. The DEGs were subjected to KEGG and GO enrichment analyses, and the hub signaling pathways and hub DEGs were identified. The results demonstrate that sixteen genes within the signal pathway associated with fatty acid metabolism were found to be significantly up-regulated. Specifically, these genes were found to mainly participate in fatty acid transport, fatty acid oxidation, and ketogenesis. Furthermore, thirteen genes that play a crucial role in glucose metabolism, particularly in the pathways of glycolysis and glycogenesis, were significantly down-regulated in the livers of overfed zebrafish. These results indicate insulin resistance and inhibition of glucose entry into liver cells in the livers of overfed zebrafish. These findings elucidate the underlying molecular basis of zebrafish diabetes induced by overfeeding and provide a model for further investigation of the pathogenesis and therapeutics of diabetes.
first_indexed 2024-03-11T00:26:21Z
format Article
id doaj.art-5c56ce49dbe34751a8612160af9d60dc
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-11T00:26:21Z
publishDate 2023-07-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-5c56ce49dbe34751a8612160af9d60dc2023-11-18T22:58:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151199410.3390/ijms241511994Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in ZebrafishGuodong Ge0Jing Ren1Guili Song2Qing Li3Zongbin Cui4Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, ChinaGuangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, ChinaGuangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, ChinaDiabetes has gradually become a serious disease that threatens human health. It can induce various complications, and the pathogenesis of diabetes is quite complex and not yet fully elucidated. The zebrafish has been widely acknowledged as a useful model for investigating the mechanisms underlying the pathogenesis and therapeutic interventions of diabetes. However, the molecular basis of zebrafish diabetes induced by overfeeding remains unknown. In this study, a zebrafish diabetes model was established by overfeeding, and the molecular basis of zebrafish diabetes induced by overfeeding was explored. Compared with the control group, the body length, body weight, and condition factor index of zebrafish increased significantly after four weeks of overfeeding. There was a significant elevation in the fasting blood glucose level, accompanied by a large number of lipid droplets accumulated within the liver. The levels of triglycerides and cholesterol in both the serum and liver exhibited a statistically significant increase. Transcriptome sequencing was employed to investigate changes in the livers of overfed zebrafish. The number of up-regulated and down-regulated differentially expressed genes (DEGs) was 1582 and 2404, respectively, in the livers of overfed zebrafish. The DEGs were subjected to KEGG and GO enrichment analyses, and the hub signaling pathways and hub DEGs were identified. The results demonstrate that sixteen genes within the signal pathway associated with fatty acid metabolism were found to be significantly up-regulated. Specifically, these genes were found to mainly participate in fatty acid transport, fatty acid oxidation, and ketogenesis. Furthermore, thirteen genes that play a crucial role in glucose metabolism, particularly in the pathways of glycolysis and glycogenesis, were significantly down-regulated in the livers of overfed zebrafish. These results indicate insulin resistance and inhibition of glucose entry into liver cells in the livers of overfed zebrafish. These findings elucidate the underlying molecular basis of zebrafish diabetes induced by overfeeding and provide a model for further investigation of the pathogenesis and therapeutics of diabetes.https://www.mdpi.com/1422-0067/24/15/11994diabetes mellituszebrafishliverRNA-seqsignaling pathway
spellingShingle Guodong Ge
Jing Ren
Guili Song
Qing Li
Zongbin Cui
Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish
International Journal of Molecular Sciences
diabetes mellitus
zebrafish
liver
RNA-seq
signaling pathway
title Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish
title_full Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish
title_fullStr Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish
title_full_unstemmed Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish
title_short Transcriptome Analysis Reveals the Molecular Basis of Overfeeding-Induced Diabetes in Zebrafish
title_sort transcriptome analysis reveals the molecular basis of overfeeding induced diabetes in zebrafish
topic diabetes mellitus
zebrafish
liver
RNA-seq
signaling pathway
url https://www.mdpi.com/1422-0067/24/15/11994
work_keys_str_mv AT guodongge transcriptomeanalysisrevealsthemolecularbasisofoverfeedinginduceddiabetesinzebrafish
AT jingren transcriptomeanalysisrevealsthemolecularbasisofoverfeedinginduceddiabetesinzebrafish
AT guilisong transcriptomeanalysisrevealsthemolecularbasisofoverfeedinginduceddiabetesinzebrafish
AT qingli transcriptomeanalysisrevealsthemolecularbasisofoverfeedinginduceddiabetesinzebrafish
AT zongbincui transcriptomeanalysisrevealsthemolecularbasisofoverfeedinginduceddiabetesinzebrafish