Aberrant expression of microRNA induced by high-fructose diet: Implications in the pathogenesis of hyperlipidemia and hepatic insulin resistance

Authors

Nettu Sud, University of Nebraska–Lincoln
Hanyuan Zhang, University of Nebraska–Lincoln
Kaichao Pan, University of Nebraska–Lincoln
Xiao Cheng, University of Nebraska–LincolnFollow
Juan Cui, University of Nebraska-LincolnFollow
Qiaozhu Su, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

3-2017

Citation

Published in Journal of Nutritional Biochemistry 43 (2017), pp. 125–131. doi: 10.1016/j.jnutbio.2017.02.003

Comments

Copyright © 2017 Elsevier Inc. Used by permission.

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.