Cardiovascular and body weight regulation changes in transgenic mice overexpressing thyrotropin-releasing hormone (TRH)
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ORIGINAL ARTICLE
Cardiovascular and body weight regulation changes in transgenic mice overexpressing thyrotropin-releasing hormone (TRH) María Silvina Landa 1,2 & Silvia Inés García 1,3,4 & Mariano Luis Schuman 1,3 & Ludmila Soledad Peres Diaz 1,3 & Maia Aisicovich 1,3 & Carlos José Pirola 1,2 Received: 11 June 2020 / Accepted: 2 September 2020 # University of Navarra 2020
Abstract Thyrotropin-releasing hormone (TRH) plays several roles as a hormone/neuropeptide. Diencephalic TRH (dTRH) participates in the regulation of blood pressure in diverse animal models, independently of the thyroid status. The present study aimed to evaluate whether chronic overexpression of TRH in mice affects cardiovascular and metabolic variables. We developed a transgenic (TG) mouse model that overexpresses dTrh. Despite having higher food consumption and water intake, TG mice showed significantly lower body weight respect to controls. Also, TG mice presented higher blood pressure, heart rate, and locomotor activity independently of thyroid hormone levels. These results and the higher urine noradrenaline excretion observed in TG mice suggest a higher metabolic rate mediated by sympathetic overflow. Cardiovascular changes were impeded by siRNA inhibition of the diencephalic Trh overexpression. Also, the silencing of dTRH in the TG mice normalized urine noradrenaline excretion, supporting the view that the cardiovascular effects of TRH involve the sympathetic system. Overall, we show that congenital dTrh overexpression leads to an increase in blood pressure accompanied by changes in body weight and food consumption mediated by a higher sympathetic overflow. These results provide new evidence confirming the participation of TRH in cardiovascular and body weight regulation. Keywords TRH . Transgenic . Hypertension . Body weight regulation . Mice . Overexpression . Sympathetic outflow . Blood pressure regulation . siRNA María Silvina Landa and Silvia Inés García contributed equally to this work. Key Points • Transgenic mice overexpressing TRH present higher blood pressure and a lower body weight despite increased food consumption and water intake. • A specific siRNA against Trh injected intracerebroventricularly normalized blood pressure. • Cardiovascular and body weight regulation changes induced by TRH overexpression are dependent on an increased sympathetic tone but not thyroid hormones. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13105-020-00765-x) contains supplementary material, which is available to authorized users. * María Silvina Landa [email protected]
2
National Scientific and Technical Research Council (CONICET), Institute of Medical Research (IDIM), Department of Molecular Genetics and Biology of Complex Diseases, Universidad de Buenos Aires, Buenos Aires, Argentina
3
National Scientific and Technical Research Council (CONICET), Institute of Medical Research (IDIM), Laboratory of Molecular Cardiology, Universidad de Buenos Aires, Buenos Aires, Argentina
4
Laboratori
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