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Role of the melanocortin system and the renin-angiotensin system on cardiorespiratory changes in rats fed with high fat diet

Grant number: 13/13118-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2013
Effective date (End): February 29, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Débora Simões de Almeida Colombari
Grantee:Guilherme Fleury Fina Speretta
Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated research grant:11/50770-1 - Neural mechanisms involved of hydroelectrolytic balance and cardiorespiratory control, AP.TEM


In the last decades, obesity has become a worldwide epidemic. Excess adipose tissue favors the development of associated diseases such as hypertension, obstructive sleep apnea and alveolar hypoventilation. Studies have shown that obesity activates the renin-angiotensin system (RAS), increased serum levels of leptin and the levels of proinflammatory cytokines, including in the central nervous system. However, the pathways and neural mechanisms involved in these responses are not yet fully elucidated. Therefore, the aim of this study is to evaluate the cardiovascular, ventilatory and metabolic changes in rats with high fat diet and to study the possible participation angiotensinergic system and the melanocortin system activated by leptin in the nucleus of the solitary tract (NTS) in these changes. For this, adult Holtzman rats (300-320 g) will undergo a high fat diet (3, 6 and 12 weeks). In each period, we will assess the ventilatory responses during chemoreflex activation in hypoxia (7% O2) and hypercapnia (7% CO2), mean arterial pressure and heart rate at baseline and the baroreflex, before and after the treatment in the NTS with melanocortin MC3 receptor antagonist/4 or changing the RAS within the NTS, by way of losartan (AT1 antagonist) injection into the NTS or by the over-expression of angiotensin II AT2 receptors in the NTS. We will also evaluate the respiratory coefficient, lipid profile, plasma levels of glucose, leptin and insulin. At the end of the experiments, the brains will be removed for gene expression in the NTS of genes related to the RAS, leptin and pro-and antiinflammatory cytokines. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SPERETTA, GUILHERME F.; RUCHAYA, PRASHANT J.; DELBIN, MARIA A.; MELO, MARIANA R.; LI, HONGWEI; MENANI, V, JOSE; SUMNERS, COLIN; COLOMBARI, EDUARDO; BASS, MIRIAN; COLOMBARI, DEBORA S. A.. Importance of All and AT2 receptors in the nucleus of the solitary tract in cardiovascular responses induced by a high-fat diet. HYPERTENSION RESEARCH, v. 42, n. 4, p. 439-449, . (13/13118-0)
SPERETTA, GUILHERME F.; LEMES, EDUARDO VIEIRA; VENDRAMINI, REGINA C.; MENANI, JOSE V.; ZOCCAL, DANIEL B.; COLOMBARI, EDUARDO; COLOMBARI, DEBORA S. A.; BASSI, MIRIAN. High-fat diet increases respiratory frequency and abdominal expiratory motor activity during hypercapnia. Respiratory Physiology & Neurobiology, v. 258, p. 32-39, . (13/17251-6, 13/13118-0)
SPERETTA, GUILHERME F.; SILVA, ANDRE A.; VENDRAMINI, REGINA C.; ZANESCO, ANGELINA; DELBIN, MARIA A.; MENANI, JOSE V.; BASSI, MIRIAN; COLOMBARI, EDUARDO; COLOMBARI, DEBORA S. A.. Resistance training prevents the cardiovascular changes caused by high-fat diet. Life Sciences, v. 146, p. 154-162, . (13/13118-0, 11/50770-1)

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