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

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


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)