Sanchez-Garrido, M.A.Ruiz-Pino, F.Pozo-Salas, A.I.Castellano, J.M.Vazquez, M.J.Luque, R.M.Tena-Sempere, M.2022-08-052022-08-052020-08-17Sanchez-Garrido MA, Ruiz-Pino F, Pozo-Salas AI, Castellano JM, Vazquez MJ, Luque RM, et al. Early overnutrition sensitizes the growth hormone axis to the impact of diet-induced obesity via sex-divergent mechanisms. Sci Rep. 2020 Aug 17;10(1):13898http://hdl.handle.net/10668/3890In addition to its essential role in the physiological control of longitudinal growth, growth-hormone (GH) is endowed with relevant metabolic functions, including anabolic actions in muscle, lipolysis in adipose-tissue and glycemic modulation. Adult obesity is known to negatively impact GH-axis, thereby promoting a vicious circle that may contribute to the exacerbation of the metabolic complications of overweight. Yet, to what extent early-overnutrition sensitizes the somatotropic-axis to the deleterious effects of obesity remains largely unexplored. Using a rat-model of sequential exposure to obesogenic insults, namely postnatal-overfeeding during lactation and high-fat diet (HFD) after weaning, we evaluated in both sexes the individual and combined impact of these nutritional challenges upon key elements of the somatotropic-axis. While feeding HFD per se had a modest impact on the adult GH-axis, early overnutrition had durable effects on key elements of the somatotropic-system, which were sexually different, with a significant inhibition of pituitary gene expression of GH-releasing hormone-receptor (GHRH-R) and somatostatin receptor-5 (SST5) in males, but an increase in pituitary GHRH-R, SST2, SST5, GH secretagogue-receptor (GHS-R) and ghrelin expression in females. Notably, early-overnutrition sensitized the GH-axis to the deleterious impact of HFD, with a significant suppression of pituitary GH expression in both sexes and lowering of circulating GH levels in females. Yet, despite their similar metabolic perturbations, males and females displayed rather distinct alterations of key somatotropic-regulators/ mediators. Our data document a synergistic effect of postnatal-overnutrition on the detrimental impact of HFD-induced obesity on key elements of the adult GH-axis, which is conducted via mechanisms that are sexually-divergent.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/OvernutritionObesityGrowth hormoneSex characteristicsHipernutriciónObesidadHormona del crecimientoCaracterísticas sexualesMetabolismoMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body WeightMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pituitary Hormones::Pituitary Hormones, Anterior::Growth HormoneMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Somatomedins::Insulin-Like Growth Factor IMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical::Models, BiologicalMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight::ObesityMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Organ SpecificityMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::OvernutritionMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats::Rats, WistarMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Peptide::Receptors, Neuropeptide::Receptors, SomatotropinMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet, High-FatMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Sex CharacteristicsMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolismresearch article32807904open access10.1038/s41598-020-70898-y2045-2322PMC7431568