title: RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders.
abstract: The paternal heredity of obesity and diabetes induced by a high-fat and/or high-sugar diet (Western-like diet) has been demonstrated through epidemiological analysis of human cohorts and experimental analysis, but the nature of the hereditary vector inducing this newly acquired phenotype is not yet well defined. Here, we show that microinjection of either testis or sperm RNA of male mice fed a Western-like diet into naive one-cell embryos leads to the establishment of the Western-like diet-induced metabolic phenotype in the resulting progenies, whereas RNAs prepared from healthy controls did not. Among multiple sequence differences between the testis transcriptomes of the sick and healthy fathers, we noted that several microRNAs had increased expression, which was of interest because this class of noncoding RNA is known to be involved in epigenetic control of gene expression. When microinjected into naive one-cell embryos, one of these small RNA, i.e., the microRNA miR19b, induced metabolic alterations that are similar to the diet-induced phenotype. Furthermore, this pathological phenotype was inherited by the offspring after crosses with healthy partners. Our results indicate that acquired food-induced trait inheritance might be enacted by RNA signalling.
authors.affiliation: Inserm, U1091, Nice, F-06108.|CNRS, UMR7277, F-06108, France.|University of Nice-Sophia Antipolis, UFR Sciences, Nice, F-06108.
authors.forename: Valérie
authors.initials: V
authors.lastname: Grandjean
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR 6079 CNRS-UNSA, Sophia Antipolis, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fourré
authors.affiliation: UMR Inra 1355, CNRS 7254, UNS, Sophia Antipolis, France.
authors.forename: Diana Andrea Fernandes
authors.initials: DA
authors.lastname: De Abreu
authors.affiliation: Inserm, U1091, Nice, F-06108.|CNRS, UMR7277, F-06108, France.|University of Nice-Sophia Antipolis, UFR Sciences, Nice, F-06108.
authors.forename: Marie-Alix
authors.initials: MA
authors.lastname: Derieppe
authors.affiliation: UMR Inra 1355, CNRS 7254, UNS, Sophia Antipolis, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Remy
authors.affiliation: Inserm, U1091, Nice, F-06108.|CNRS, UMR7277, F-06108, France.|University of Nice-Sophia Antipolis, UFR Sciences, Nice, F-06108.
authors.forename: Minoo
authors.initials: M
authors.lastname: Rassoulzadegan
mesh_terms: D000818:Animals; D004032:Diet / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D040582:Inheritance Patterns; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology* / Q000378:metabolism*; D035683:MicroRNAs / Q000008:administration & dosage / Q000235:genetics; D008845:Microinjections; D009765:Obesity / Q000209:etiology* / Q000378:metabolism*; D012313:RNA / Q000008:administration & dosage / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012313:RNA