Aberrant expression of microRNA induced by high-fructose diet: implications in the pathogenesis of hyperlipidemia and hepatic insulin resistance |
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| Affiliation: | 1. The Department of Nutrition and Health Sciences, University of Nebraska–Lincoln, Lincoln, NE 68583-0806, USA;2. Department of Computer Science & Engineering, University of Nebraska–Lincoln, Lincoln, NE 68583-0806, USA;1. Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH, USA;2. Center of Environmental Genetics, University of Cincinnati Medical Center, Cincinnati, OH, USA;3. Cincinnati Cancer Center, Cincinnati, OH, USA;4. Department of Pharmacology and Cell Biophysics Pharmacology, University of Cincinnati Medical Center, Cincinnati, OH, USA;5. Cincinnati Veteran Affairs Medical Center, Cincinnati, OH, USA;1. Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy & Health Sciences, University of the Pacific, Stockton, CA 95211, USA;2. Department of Pharmacology Toxicology and Therapeutic Chemistry, School of Pharmacy and Food Sciences, University of Barcelona;3. IBUB (Institute of Biomedicine, University of Barcelona);4. CIBERobn (Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición);1. Department of Molecular Biology and Genetics, Faculty of Sciences and Arts, Bulent Ecevit University, Zonguldak, Turkey;2. Department of Dermatology, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey;3. Department of Medical Genetics, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey;1. CENEXA, Centro de Endocrinología Experimental y Aplicada (UNLP-CONICET La Plata), Argentina;2. CIC, Centro de Investigaciones Cardiovasculares (UNLP-CONICET La Plata), Argentina;3. Farmacología Básica, Facultad de Ciencias Médicas UNLP, La Plata, Argentina;1. Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan;2. Department of Hygiene, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan;3. Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, 470-1192, Japan;4. Deparment of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan;5. Department of Chemistry, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan;6. Department of Preventive Medical Sciences, Fujita Health University School of Health Sciences, Toyoake, 470-1192, Japan |
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| 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. |
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