RNA-seq analysis of the hypothalamic transcriptome reveals the networks regulating physiopathological progress in the diabetic GK rat

Meng, Yuhuan; Guan, Yujia; Zhang, Wenlu; Wu, Yue; Jia, Huanhuan; Zhang, Yu; Zhang, Xiuqing; Du, Hongli; Wang, Xiaoning

doi:10.1038/srep34138

Cited by 14 publications

(10 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lee [33] found this enzyme in the ovary of rats. Animal studies have shown that ADCY3 plays an important role in the regulation of the hypothalamus of rats [34]. In addition, ADCY3 is highly expressed in olfactory epithelial cells [35] and is primarily responsible for the detection of odors.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analyses of the Hypothalamic-Pituitary-Gonadal Axis Identify Candidate Genes Related to Egg Production in Xinjiang Yili Geese

Zhao

Chen

et al. 2020

Animals

View full text Add to dashboard Cite

The study was conducted to investigate the transcriptomic differences of the hypothalamic-pituitary-gonadal axis between Xinjiang Yili geese with high and low egg production and to find candidate genes regulating the egg production of Xinjiang Yili geese. The 8 selected Xinjiang Yili Geese with high or low egg production (4 for each group) were 3 years old, with good health, and under the same feeding condition. High-throughput sequencing technology was used to sequence cDNA libraries of the hypothalami, pituitary glands, and ovaries. The sequencing data were compared and analyzed, and the transcripts with significant differences were identified and analyzed with bioinformatics. The study showed that the transcriptome sequencing data of the 24 samples contained a total of 1,176,496,146 valid reads and 176.47 gigabase data. Differential expression analyses identified 135, 56, and 331 genes in the hypothalami, pituitary glands, and ovaries of Xinjiang Yili geese with high and low egg production. Further annotation of these differentially expressed genes in the non-redundant protein sequence database (Nr) revealed that 98, 52, and 309 genes were annotated, respectively. Through the annotations of GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) databases, 30 candidate genes related to the egg production of Xinjiang Yili geese were preliminarily selected. The gap junction, focal adhesion, and ECM-receptor interaction signaling pathways were enriched with the hypothalamic, pituitary, and ovarian differentially expressed genes, and the calcium signaling pathway was enriched with the pituitary and ovarian differentially expressed genes. Thus, these pathways in the hypothalamic-pituitary-gonadal axis may play an important role in regulating egg production of Xinjiang Yili geese. The results provided the transcriptomic information of the hypothalamic-pituitary-gonadal axis of Xinjiang Yili geese and laid the theoretical basis for revealing the molecular mechanisms regulating the egg-laying traits of Xinjiang Yili geese.

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptomic Analyses of the Hypothalamic-Pituitary-Gonadal Axis Identify Candidate Genes Related to Egg Production in Xinjiang Yili Geese

Zhao

Chen

et al. 2020

Animals

View full text Add to dashboard Cite

show abstract

“…DEGs analysis revealed that 726 genes were significantly altered in GK rats compared with Wistar rats. Of these DEGs, 507 genes were also identified in our previous study of the hypothalamic transcriptome in GK rats (Meng et al, 2016). The partial differences of GK rat transcriptomic profiles in two studies might be related to the change in the breeding environment (Portha et al, 2012).…”

Section: Discussionmentioning

confidence: 91%

“…Research has shown that hypothalamic dysfunctions contribute to the development of chronic conditions, such as T2D (Jais & Bruning, 2017; Chowen et al, 2016). We previously detected the disorder of transcriptome in the hypothalamus through RNA sequencing (RNA-Seq) analysis, which might be associated with pathogenesis in diabetic GK rats (Meng et al, 2016). Physical activity is a critical element in the management and prevention of T2D by improving blood glucose and insulin action (De Feo & Schwarz, 2013).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic responses of hypothalamus to acute exercise in type 2 diabetic Goto-Kakizaki rats

Meng

Lin

et al. 2019

PeerJ

Self Cite

View full text Add to dashboard Cite

The hypothalamus has an integral role in energy homeostasis regulation, and its dysfunctions lead to the development of type 2 diabetes (T2D). Physical activity positively affects the prevention and treatment of T2D. However, there is not much information on the adaptive mechanisms of the hypothalamus. In this study, RNA sequencing was used to determine how acute exercise affects hypothalamic transcriptome from both type 2 diabetic Goto-Kakizaki (GK) and control Wistar rats with or without a single session of running (15 m/min for 60 min). Through pairwise comparisons, we identified 957 differentially expressed genes (DEGs), of which 726, 197, and 98 genes were found between GK and Wistar, exercised GK and GK, and exercised Wistar and Wistar, respectively. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment revealed that lipid metabolism-related terms and pathways were enriched in GK and exercised GK rats, and nervous system related terms and pathways were enriched in exercised GK and Wistar rats. Furthermore, 45 DEGs were associated with T2D and related phenotypes according to the annotations in the Rat Genome Database. Among these 45 DEGs, several genes (Plin2, Cd36, Lpl, Wfs1, Cck) related to lipid metabolism or the nervous system are associated with the exercise-induced benefits in the hypothalamus of GK rats. Our findings might assist in identifying potential therapeutic targets for T2D prevention and treatment.

show abstract

“…The genome sequencing of 10 GK rats and 10 Wistar rats (8 weeks old) were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All rats used in this study were same with our previous study (Meng et al, 2016), which were approved by the institutional review board of the Guangdong Key Laboratory of Laboratory Animals. All protocols were carried out in accordance with the approved guidelines of the Institutional Animal Care and Use Committee, Ethic Certificate No: IACUC2014029.…”

Section: Methodsmentioning

confidence: 99%

Integrative Analysis of Genome and Expression Profile Data Reveals the Genetic Mechanism of the Diabetic Pathogenesis in Goto Kakizaki (GK) Rats

et al. 2019

Self Cite

View full text Add to dashboard Cite

The Goto Kakizaki (GK) rats which can spontaneously develop type 2 diabetes (T2D), are generated by repeated inbreeding of Wistar rats with glucose intolerance. The glucose intolerance in GK rat is mainly attributed to the impairment in glucose-stimulated insulin secretion (GSIS). In addition, GK rat display a decrease in beta cell mass, and a change in insulin action. However, the genetic mechanism of these features remain unclear. In the present study, we analyzed the population variants of GK rats and control Wistar rats by whole genome sequencing and identified 1,839 and 1,333 specific amino acid changed (SAAC) genes in GK and Wistar rats, respectively. We also detected the putative artificial selective sweeps (PASS) regions in GK rat which were enriched with GK fixed variants and were under selected in the initial diabetic-driven derivation by homogeneity test with the fixed and polymorphic sites between GK and Wistar populations. Finally, we integrated the SAAC genes, PASS region genes and differentially expressed genes in GK pancreatic beta cells to reveal the genetic mechanism of the impairment in GSIS, a decrease in beta cell mass, and a change in insulin action in GK rat. The results showed that Slc2a2 gene was related to impaired glucose transport and Adcy3, Cacna1f, Bmp4, Fam3b, and Ptprn2 genes were related to Ca2+ channel dysfunction which may responsible for the impaired GSIS. The genes Hnf4g, Bmp4, and Bad were associated with beta cell development and may be responsible for a decrease in beta cell mass while genes Ide, Ppp1r3c, Hdac9, Ghsr, and Gckr may be responsible for the change in insulin action in GK rats. The overexpression or inhibition of Bmp4, Fam3b, Ptprn2, Ide, Hnf4g, and Bad has been reported to change the glucose tolerance in rodents. However, the genes Bmp4, Fam3b, and Ptprn2 were found to be associated with diabetes in GK rats for the first time in the present study. Our findings provide a comprehensive genetic map of the abnormalities in GK genome which will be helpful in understand the underlying genetic mechanism of pathogenesis of diabetes in GK rats.

show abstract

RNA-seq analysis of the hypothalamic transcriptome reveals the networks regulating physiopathological progress in the diabetic GK rat

Cited by 14 publications

References 59 publications

Transcriptomic Analyses of the Hypothalamic-Pituitary-Gonadal Axis Identify Candidate Genes Related to Egg Production in Xinjiang Yili Geese

Transcriptomic Analyses of the Hypothalamic-Pituitary-Gonadal Axis Identify Candidate Genes Related to Egg Production in Xinjiang Yili Geese

Transcriptomic responses of hypothalamus to acute exercise in type 2 diabetic Goto-Kakizaki rats

Integrative Analysis of Genome and Expression Profile Data Reveals the Genetic Mechanism of the Diabetic Pathogenesis in Goto Kakizaki (GK) Rats

Contact Info

Product

Resources

About