title: Perturbation of hypothalamic microRNA expression patterns in male rats after metabolic distress: impact of obesity and conditions of negative energy balance.
abstract: The hypothalamus plays a crucial role in body weight homeostasis through an intricate network of neuronal circuits that are under the precise regulation of peripheral hormones and central transmitters. Although deregulated function of such circuits might be a major contributing factor in obesity, the molecular mechanisms responsible for the hypothalamic control of energy balance remain partially unknown. MicroRNAs (miRNAs) have been recognized as key regulators of different biological processes, including insulin sensitivity and glucose metabolism. However, the roles of miRNA pathways in the control of metabolism have been mostly addressed in peripheral tissues, whereas the potential deregulation of miRNA expression in the hypothalamus in conditions of metabolic distress remains as yet unexplored. In this work, we used high-throughput screening to define to what extent the hypothalamic profiles of miRNA expression are perturbed in two extreme conditions of nutritional stress in male rats, namely chronic caloric restriction and high-fat diet-induced obesity. Our analyses allowed the identification of sets of miRNAs, including let-7a, mir-9*, mir-30e, mir-132, mir-145, mir-200a, and mir-218, whose expression patterns in the hypothalamus were jointly altered by caloric restriction and/or a high-fat diet. The predicted targets of these miRNAs include several elements of key inflammatory and metabolic pathways, including insulin and leptin. Our study is the first to disclose the impact of nutritional challenges on the hypothalamic miRNA expression profiles. These data will help to characterize the molecular miRNA signature of the hypothalamus in extreme metabolic conditions and pave the way for targeted mechanistic analyses of the involvement of deregulated central miRNAs pathways in the pathogenesis of obesity and related disorders.
authors: Department of Medicine (S.S.-A., L.P.-B., F.C.), School of Health Science, University of A Coruña, Campus de Oza, 15006 A Coruña, Spain; Instituto de Investigación Biomédica de A Coruña (S.S.-A., L.P.-B., F.C.), Xubias de Arriba, 84, 15006 A Coruña, Spain; Division of Endocrinology (L.P.-B., F.C.), Complexo Hospitalario Universitario de A Coruña (CHUAC), 15006 A Coruña, Spain; and Department of Cell Biology (M.M.-L., M.T.-S.), Physiology and Immunology, University of Córdoba, Centro de Investigación Biomédica en Red, Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, and Instituto Maimónides de Investigación Biomédica/Hospital Universitario Reina Sofía, 14004 Córdoba, Spain.
authors: Susana
authors: S
authors: Sangiao-Alvarellos
authors: Lara
authors: L
authors: Pena-Bello
authors: María
authors: M
authors: Manfredi-Lozano
authors: Manuel
authors: M
authors: Tena-Sempere
authors: Fernando
authors: F
authors: Cordido
mesh_terms: D000375:Aging; D000818:Animals; D001067:Appetite Depressants / Q000627:therapeutic use; D001823:Body Composition; D031204:Caloric Restriction / Q000009:adverse effects; D019295:Computational Biology; D059305:Diet, High-Fat / Q000009:adverse effects; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000097:blood / Q000627:therapeutic use; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014886:Weaning
chemical_list: D001067:Appetite Depressants; D020738:Leptin; D035683:MicroRNAs