Comprehensive Transcriptome Analyses of the Fructose-Fed Syrian Golden Hamster Liver Provides Novel Insights into Lipid Metabolism

Abstract

Dyslipidemia has been widely proven to contribute to cardiovascular diseases and other metabolic disorders, especially in insulin resistance and type 2 diabetes. The overproduction of VLDL is a significant characteristic of dyslipidemia, indicating the dysfunction of hepatic lipid metabolism, from triglyceride synthesis to transport. The fructose-fed Syrian golden hamster is an established animal model for the study of VLDL assembly with insulin resistance, however, it remains unknown how VLDL production is regulated at the transcriptional level due to the absence of a complete hamster genome. Here, we performed deep sequencing and constructed an mRNA-miRNA-lncRNA interaction network of Syrian golden hamster liver in order to reveal the global transcription profile and find potential RNA molecular regulation of VLDL production. We identified 4,450 novel multi-exon hamster lncRNAs and 755 miRNAs expressed in liver. Additionally, 146 differentially expressed coding genes, 27 differentially expressed lncRNA genes, as well as 16 differentially expressed miRNAs were identified. We then constructed an mRNA-miRNA-lncRNA interaction network that may potentially regulate VLDL production, and interestingly found several microRNA-centered regulatory networks. In order to verify our interpretation, miR-486 was selected for further experiments. Overexpression or down-regulation of miR-486 in fructose-fed hamsters resulted in altered hepatic expression of proteins involved in VLDL production, and in modulated levels of circulating VLDL. Our findings implicated that miR-486 is a potential regulator of circulating VLDL levels. These results provide new insights and a valuable resource for further study of the molecular mechanisms of VLDL secretion.

Host Genetic Background and Gut Microbiota Contribute to Differential Metabolic Responses to Fructose Consumption in Mice

“…Our recent systems nutrigenomics study unraveled the impact of fructose on transcriptome, epigenome and gene-gene interactions in the hypothalamus, which is the main regulator of metabolism (2). Additionally, studies on the liver and adipose tissues have also revealed fructose-induced alterations in genes involved in several aspects of systemic metabolism (3)(4)(5). Interestingly, genetically diverse mouse strains demonstrate disparate metabolic responses to fructose consumption, a finding reproducible across multiple studies, including ours (5,6).…”

“…3 Sample size n=4-6/group/mouse strain. 4 Full lists of correlated genes are in Supplemental Table 1 and enriched pathways are in Supplemental Table 2.…”

MiR-27a-5p Increases Steer Fat Deposition Partly by Targeting Calcium-sensing Receptor (CASR)

“…In this study, bta-miR-27a-5p was expressed in high abundance, followed by bta-miR-486, bta-miR-450b, bta-miR-424-5p and bta-miR-34a in the BL library compared to the SL library. Previous studies reported that miR-486 regulates lipid metabolism through the PI3K-Akt-signaling pathway by targeting the phosphorylation of Akt and tensin homolog and FoxO1 38 , 41 , 42 . MiR-34a regulates the activity of AMP kinase, a known regulator of energy metabolism, by suppressing SIRT1 43 , and has been reported to emerge as a specific miRNA modulated lipid metabolism in the liver 44 .…”

Transcriptome Profile Analysis Reveals an Estrogen Induced LncRNA Associated with Lipid Metabolism and Carcass Traits in Chickens (Gallus Gallus)

“…Both lncRNAs and miRNAs are endogenously expressed regulators of gene expression [18]. Given the complex interaction among lncRNAs, miRNAs and mRNAs, it is necessary to integrate these datasets to further reveal the regulatory mechanisms among lncRNAs-mRNAs-miRNAs [19].…”