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Effects of PPAR-gamma or PPAR-alpha agonists on the metabolic programming induced by maternal caloric restriction during pregnancy and lactation

Grant number: 17/20742-2
Support Opportunities:Regular Research Grants
Duration: April 01, 2018 - December 31, 2019
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Gabriel Forato Anhê
Grantee:Gabriel Forato Anhê
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


Background: Caloric restriction (CR) of 50% during pregnancy and lactation may raise maternal corticosterone levels and relative adrenal weight. This corticosterone excess programs long-term consequences in the offspring such as increased arterial stiffness and glucose intolerance. Interestingly, the phenotype programming originated by caloric restriction is partially prevented by treating the mothers with drugs that inhibit corticosterone synthesis. It is not clear however, if other drugs that blunt the hypothalamus-pituitary-adrenal (HPA) axis are also able to prevent the phenotype programming induced by maternal CR. In this sense, PPAR-gamma and PPAR-alpha agonists (originally used to control blood glucose and triglycerides levels, respectively) are known to reduce the HPA axis activity. Aim: determine if the use of PPAR-gamma or PPAR-alpha agonists in pregnant rats subjected to CR during pregnancy and lactation is able to interfere in the metabolic programming of the offspring. Methods: Pregnant Wistar rats (P15) will be assigned to two different protocols, each one consisted of 4 experimental groups. In experiment 1, groups will be: CTL (pregnant rats left untreated receiving ad libitum chow); CR (pregnant rats left untreated receiving 50% caloric restriction); Gem (pregnant rats treated with Gemfibrozil receiving ad libitum chow) and CR+Gem (pregnant rats treated with Gemfibrozil receiving 50% caloric restriction). In experiment 2, the CTL and CR groups will be the same for experiment 1. Additional parallel groups will be Pio (pregnant rats treated with Pioglitazone receiving ad libitum chow) and CR+Pio (pregnant rats treated with Pioglitazone receiving 50% caloric restriction). Treatment will be performed until the 21st day after delivery (weaning). Female offspring will be used with 90 and 180 days of age. Offspring will be subjected to VLDL production assay, glucose and insulin tolerance tests and pancreatic isolation for insulin secretion. Pregnant rats will also be subjected to analysis (P19) of circulating ACTH and corticosterone. Adrenal glands and hypothalamus will be removed for qPCR determination of STAR, ACTHR, POMC and CRH mRNAs. (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)
E-LACERDA, RODRIGO RODRIGUES; TEIXEIRA, CAIO JORDAO; BORDIN, SILVANA; ANTUNES, EDSON; ANHE, GABRIEL FORATO. Maternal Obesity in Mice Exacerbates the Allergic Inflammatory Response in the Airways of Male Offspring. NUTRIENTS, v. 11, n. 12, . (16/22722-6, 17/20742-2, 17/15175-1, 13/07607-8, 15/18997-7)
VERONESI, VANESSA BARBOSA; PIOLI, MARIANA RODRIGUES; DE SOUZA, DAILSON NOGUEIRA; TEIXEIRA, CAIO JORDAO; MURATA, GILSON MASAHIRO; SANTOS-SILVA, JUNIA CAROLINA; HECHT, FERNANDA BALLERINI; VICENTE, JULIA MODESTO; BORDIN, SILVANA; ANHE, GABRIEL FORATO. Agomelatine reduces circulating triacylglycerides and hepatic steatosis in fructose-treated rats. BIOMEDICINE & PHARMACOTHERAPY, v. 141, . (16/13138-9, 13/07607-8, 15/23285-6, 20/06397-3, 17/20742-2, 19/03196-0)

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