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Influence of unsaturated high-fat diet in the lipid energy metabolism regulation and in the cardiac dysfunction in rats with supravalvar aortic stenosis

Grant number: 12/19679-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2013
Effective date (End): February 28, 2017
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Antonio Carlos Cicogna
Grantee:Loreta Casquel de Tomasi
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Associated scholarship(s):14/06030-1 - Influence of high fat diets on lipid energy metabolism and cardiac dysfunction in rodents during chronic cardiac stress, BE.EP.DR

Abstract

Cardiac remodeling (CR) occurs in response to certain types of aggression, such as pressure overload, and it can be clinically manifested by changes in size, shape and function of the heart. In the model of supravalvar aortic stenosis (SVAS) in rats, echocardiographic studies have shown that, after 2 and 6 weeks of SVAS induction, rats develop left ventricular hypertrophy, diastolic dysfunction and improvement of systolic function. After the 12th week the deterioration of systolic performance occurs and around the 20th week the signs of heart failure (HF) appear. Several factors, such as changes in energy metabolism, may contribute to cardiac dysfunction in the experimental model of SVAS. In the adult heart about 60-70% of the energy used in the contraction and relaxation process is obtained from the beta oxidation of fatty acids, and the contribution of the glycolytic pathway is around 30-40%. In pathological cardiac hypertrophy, with or without HF, change occurs in the use of myocardial energy substrate evidenced by increased glucose capture and utilization. In addition, there is downregulation of beta oxidation by reduction of proteins involved in the capture and oxidation of fatty acids and also an increase in metabolic stress sensors. The administration of a diet rich in unsaturated fatty acids could provide the ligand to stimulate an increase in the expression of proteins involved in fatty acid metabolism, allowing greater capture and utilization of lipids, reducing or delaying the metabolic dysfunction and the mechanical one that occur during the progression of pathological cardiac remodeling. There are few studies that evaluated the relationship among high-fat diet, energy metabolism and cardiac function in models of hypertrophy by pressure overload. There are no studies that evaluated the effect of hyperlipidic dietary treatment on energy metabolism and cardiac function after the establishment of ventricular hypertrophy accompanied by diastolic dysfunction. This study aims to test the hypothesis that the increase in the unsaturated fatty acid supply attenuates the metabolic alteration and the cardiac function impairment in rats with left ventricular hypertrophy and diastolic dysfunction by aortic stenosis. This attenuation is due to the increased expression of proteins involved in the lipid energy metabolism regulation.

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 TOMASI, LORETA CASQUEL; SALOME CAMPOS, DIJON HENRIQUE; SANT'ANA, PAULA GRIPPA; OKOSHI, KATASHI; PADOVANI, CARLOS ROBERTO; MURATA, GILSON MASAHIRO; NGUYEN, SON; KOLWICZ, JR., STEPHEN C.; CICOGNA, ANTONIO CARLOS. Pathological hypertrophy and cardiac dysfunction are linked to aberrant endogenous unsaturated fatty acid metabolism. PLoS One, v. 13, n. 3 MAR 1 2018. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
TOMASI, Loreta Casquel de. Influência da dieta hiperlipídica insaturada na regulação do metabolismo energético lipídico e na disfunção cardíaca de ratos com estenose aórtica supravalvar. 2017. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Medicina..

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