Effect of PPAR-gamma or PPAR-alpha agonists on the metabolic programing induced by maternal caloric restriction

• Grant number: 16/13138-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2018
• End date: July 31, 2020
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Silvana Auxiliadora Bordin da Silva
• Grantee: Vanessa Barbosa Veronesi
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Caloric Restriction of 50% (CR) during the third week of rat pregnancy increases corticosterone levels and adrenal weight. The corticosterone excess programs several changes in the offspring such as arterial stiffness and glucose intolerance. The programming of vascular changes induced by CR can be avoided with drugs that blunt corticosterone synthesis during pregnancy. However, it is not precisely described if the suppression of the Hypothalamus-Pituitary-Adrenal (HPA) axis in caloric restricted pregnant rats can also interfere with the programming of the metabolic changes. Apart of this, PPAR-gamma and PPAR-alpha agonists are known to reduce the HPA axis activity and to be well tolerated by pregnant rats. Objective: Clarify whether the use of PPAR-gamma (rosiglitazone) or PPAR-alpha (gemfibrozila) agonists in pregnant rats subjected to CR may prevent metabolic programming. Methods: Pregnant Wistar rats (15th day) will be assigned to the following groups: CTL (standard chow ad libitum); CR (50% caloric restriction between the 15th day of pregnancy and the 21st day of lactation); CR+Rosi (rats subjected to CR concomitantly with Rosiglitazone treatment) and CR+Gem (rats subjected to CR concomitantly with gemfibrozila treatment. Female offspring will be subjected to glucose and insulin tolerance tests, VLDL production assay and insulin secretion by isolated islets. Maternal analysis will be consisted of measurement of ACTH and corticosterone levels at the 19th day of pregnancy. Genes related to corticosterone synthesis (STAR and ACTHR) and HPA axis (CRH and POMC) will evaluated in maternal adrenal glands and hypothalamus, respectively. (AU)

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)

DE SOUZA, DAILSON NOGUEIRA; TEIXEIRA, CAIO JORDAO; VERONESI, VANESSA BARBOSA; MURATA, GILSON MASAHIRO; SANTOS-SILVA, JUNIA CAROLINA; HECHT, FERNANDA BALLERINI; VICENTE, JULIA MODESTO; BORDIN, SILVANA; ANHE, GABRIEL FORATO. Dexamethasone programs lower fatty acid absorption and reduced PPAR-gamma and fat/CD36 expression in the jejunum of the adult rat offspring. Life Sciences, v. 265, JAN 15 2021. (13/07607-8, 20/06397-3, 19/03196-0, 16/13138-9, 15/23285-6)

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, SEP 2021. (16/13138-9, 13/07607-8, 15/23285-6, 20/06397-3, 17/20742-2, 19/03196-0)

HECHT, FERNANDA BALLERINI; TEIXEIRA, CAIO JORDAO; DE SOUZA, DAILSON NOGUEIRA; NUNES MESQUITA, FILIPHE DE PAULA; DO VAL ROSO, RYANA ELYZABETH; SODRE, FRHANCIELLY SHIRLEY; VERONESI, VANESSA BARBOSA; DA ROCHA, DEBORAH FABIANA; DANTAS DE MENEZES, YAN GUIDA; PIOLI, MARIANA RODRIGUES; et al. Antenatal corticosteroid therapy modulates hepatic AMPK phosphorylation and maternal lipid metabolism in early lactating rats. BIOMEDICINE & PHARMACOTHERAPY, v. 144, DEC 2021. (19/03196-0, 13/07607-8, 20/09717-9, 16/13138-9, 20/06397-3)