title: MicroRNA Expression Signature Is Altered in the Cardiac Remodeling Induced by High Fat Diets.
abstract: Recent studies have revealed the involvement of microRNAs (miRNAs) in the control of cardiac hypertrophy and myocardial function. In addition, several reports have demonstrated that high fat (HF) diet induces cardiac hypertrophy and remodeling. In the current study, we investigated the effect of diets containing different percentages of fat on the cardiac miRNA expression signature. To address this question, male C57Bl/6 mice were fed with a low fat (LF) diet or two HF diets, containing 45 kcal% fat (HF45%) and 60 kcal% fat (HF60%) for 10 and 20 weeks. HF60% diet promoted an increase on body weight, fasting glycemia, insulin, leptin, total cholesterol, triglycerides, and induced glucose intolerance. HF feeding promoted cardiac remodeling, as evidenced by increased cardiomyocyte transverse diameter and interstitial fibrosis. RNA sequencing analysis demonstrated that HF feeding induced distinct miRNA expression patterns in the heart. HF45% diet for 10 and 20 weeks changed the abundance of 64 and 26 miRNAs in the heart, respectively. On the other hand, HF60% diet for 10 and 20 weeks altered the abundance of 27 and 88 miRNAs in the heart, respectively. Bioinformatics analysis indicated that insulin signaling pathway was overrepresented in response to HF diet. An inverse correlation was observed between cardiac levels of GLUT4 and miRNA-29c. Similarly, we found an inverse correlation between expression of GSK3β and the expression of miRNA-21a-3p, miRNA-29c-3p, miRNA-144-3p, and miRNA-195a-3p. In addition, miRNA-1 overexpression prevented cardiomyocyte hypertrophy. Taken together, our results revealed differentially expressed miRNA signatures in the heart in response to different HF diets. J. Cell. Physiol. 231: 1771-1783, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Anatomy, Laboratory of Cell Biology and Functional Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Elaine Castilho
authors.initials: EC
authors.lastname: Guedes
authors.affiliation: Centro de Oncologia Molecular, Hospital Sírio-Libanês, Sao Paulo, Brazil.|Department of Biochemistry, Chemistry Institute, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Gustavo Starvaggi
authors.initials: GS
authors.lastname: França
authors.affiliation: Department of Anatomy, Laboratory of Cell Biology and Functional Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Caroline Antunes
authors.initials: CA
authors.lastname: Lino
authors.affiliation: Centro de Oncologia Molecular, Hospital Sírio-Libanês, Sao Paulo, Brazil.
authors.forename: Fernanda Christtanini
authors.initials: FC
authors.lastname: Koyama
authors.affiliation: Department of Anatomy, Laboratory of Cell Biology and Functional Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Luana do Nascimento
authors.initials: Ldo N
authors.lastname: Moreira
authors.affiliation: Department of Anatomy, Laboratory of Cell Biology and Functional Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Juliana Gomes
authors.initials: JG
authors.lastname: Alexandre
authors.affiliation: Department of Anatomy, Laboratory of Cell Biology and Functional Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Maria Luiza M
authors.initials: ML
authors.lastname: Barreto-Chaves
authors.affiliation: Centro de Oncologia Molecular, Hospital Sírio-Libanês, Sao Paulo, Brazil.
authors.forename: Pedro Alexandre Favoretto
authors.initials: PA
authors.lastname: Galante
authors.affiliation: Department of Anatomy, Laboratory of Cell Biology and Functional Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Gabriela Placoná
authors.initials: GP
authors.lastname: Diniz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D019295:Computational Biology; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000235:genetics / Q000378:metabolism; D005355:Fibrosis; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D035683:MicroRNAs; C495693:Slc2a4 protein, mouse; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3