title: Aberrant expression of microRNA induced by high-fructose diet: implications in the pathogenesis of hyperlipidemia and hepatic insulin resistance.
abstract: Fructose is a highly lipogenic sugar that can alter energy metabolism and trigger metabolic disorders. In the current study, microRNAs (miRNAs) altered by a high-fructose diet were comprehensively explored to elucidate their significance in the pathogenesis of chronic metabolic disorders. miRNA expression profiling using small noncoding RNA sequencing revealed that 19 miRNAs were significantly upregulated and 26 were downregulated in the livers of high-fructose-fed mice compared to chow-fed mice. Computational prediction and functional analysis identified 10 miRNAs, miR-19b-3p, miR-101a-3p, miR-30a-5p, miR-223-3p, miR-378a-3p, miR-33-5p, miR-145a-3p, miR-128-3p, miR-125b-5p and miR-582-3p, assembled as a regulatory network to potentially target key genes in lipid and lipoprotein metabolism and insulin signaling at multiple levels. qRT-PCR analysis of their potential target genes [IRS-1, FOXO1, SREBP-1c/2, ChREBP, insulin-induced gene-2 (Insig-2), microsomal triglyceride transfer protein (MTTP) and apolipoprotein B (apoB)] demonstrated that fructose-induced alterations of miRNAs were also reflected in mRNA expression profiles of their target genes. Moreover, the miRNA profile induced by high-fructose diet differed from that induced by high-fat diet, indicating that miRNAs mediate distinct pathogenic mechanisms in dietary-induced metabolic disorders. This study presents a comprehensive analysis of a new set of hepatic miRNAs, which were altered by high-fructose diet and provides novel insights into the interaction between miRNAs and their target genes in the development of metabolic syndrome.
authors.affiliation: The Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0806, USA.
authors.forename: Neetu
authors.initials: N
authors.lastname: Sud
authors.affiliation: Department of Computer Science & Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583-0806, USA.
authors.forename: Hanyuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0806, USA.
authors.forename: Kaichao
authors.initials: K
authors.lastname: Pan
authors.affiliation: The Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0806, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Computer Science & Engineering, University of Nebraska-Lincoln, Lincoln, NE 68583-0806, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Cui
authors.affiliation: The Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0806, USA. Electronic address: qsu2@unl.edu.
authors.forename: Qiaozhu
authors.initials: Q
authors.lastname: Su
mesh_terms: D000818:Animals; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D005632:Fructose / Q000009:adverse effects*; D005786:Gene Expression Regulation; D006949:Hyperlipidemias / Q000209:etiology / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats
chemical_list: C546119:MIRN378 microRNA, mouse; D035683:MicroRNAs; D005632:Fructose
keywords: Energy metabolic pathways; Fructose; High-fat diet; Metabolic syndrome; microRNAs