Banca de DEFESA: CICERA ÉDNA BARBOSA DAVID

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : CICERA ÉDNA BARBOSA DAVID
DATE: 27/07/2023
TIME: 14:00
LOCAL: FAMED
TITLE:

INVESTIGATION OF THE EFFECTS OF CALORIC RESTRICTION ON OXIDATIVE STRESS, MITOCHONDRIAL FUNCTION AND LIPIDOMA DURING ISOPROTERENOL-INDUCED CARDIAC HYPERTROPHY IN MICE

KEY WORDS:

Palmitoyl-carnitine. Reactive Oxygen Species. Antioxidants. F_oF₁ATP_ase/ATP_synthase. Cardiolipin.

PAGES: 129
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Cardiac hypertrophy is a compensatory response of the heart to an increase in volume or blood pressure. Although initially a beneficial response, it often leads to hypertrophic cardiomyopathy and heart failure. Studies indicate that cardiac hypertrophy induces a metabolic shift leading to a preferential consumption of glucose in relation to fatty acids. Caloric restriction, a dietary procedure that promotes health benefits and prolongs life expectancy in many organisms, produces effects involving improvement in energy metabolism and oxidative stress, in which mitochondria play a central role. In this work, the hypothesis was raised that part of the beneficial effects of caloric restriction is due to changes in lipid content, maintenance of mitochondrial and redox functions, and that together, these effects would induce the prevention of cardiac hypertrophy. In this work, the hypothesis was raised that part of the beneficial effects of caloric restriction is due to changes in lipid content, maintenance of mitochondrial and redox functions, and that together, these effects would induce the prevention of cardiac hypertrophy. To investigate these effects, a protocol for the induction of caloric restriction in mice was performed based on the average consumption of the standard diet of mice fed ad libitum for 2 weeks. The animals were then randomly divided into two groups: ad libitum intake (AL) and fed 60% of the mean calorie intake (CR) for an additional 4 weeks. Cardiac hypertrophy was induced by isoproterenol (ISO) (30 mg/kg/day) for 8 days. Mice treated with ISO had an increased heart weight/tibial length ratio and increased cardiomyocyte cross-sectional area. These hypertrophic markers were significantly reduced in ISO-treated CR mice. Mitochondria isolated from hypertrophic hearts produced significantly higher levels of H₂O₂ (when succinate was used without the presence of rotenone). This effect was blocked by CR. Concomitantly, cardiac hypertrophy inhibited the activity of enzymes, MnSOD, GPx, and GST, reduced rates of mitochondrial respiratory control and decreased the ATPase activity. These effects were also avoided by CR. To obtain information on how CR can interfere with hypertrophy-induced metabolic changes, cardiac lipidome was also studied. CR protected against changes in several triglycerides containing saturated fatty acids observed in hypertrophic samples. Cardiac hypertrophy induced an increase in ceramides, phosphoethanolamines and acylcarnitines (12:0, 14:0, 16:0 and 18:0), and promoted mitochondrial damage observed by swelling secondary to calcium absorption. These changes were prevented by caloric restriction. Together, these data demonstrate that hypertrophy promotes oxidative stress, mitochondrial disorders, and alters cardiac lipidome. These changes are prevented (at least partially) by in vivo caloric restriction intervention. These findings could have promising implications for the development of new treatment strategies to protect the heart against hypertrophy and its complications. However, more research is needed to deepen our understanding of the exact mechanisms by which calorie restriction exerts its beneficial effects on the heart.

BANKING MEMBERS:
Externa à Instituição - JANAÍNA ESMERALDO ROCHA
Externa à Instituição - ANNA LIDIA NUNES VARELA
Externo à Instituição - FRANCISCO ASSIS BEZERRA DA CUNHA
Interno - FRANCISCO NASCIMENTO PEREIRA JUNIOR
Presidente - HEBERTY DI TARSO FERNANDES FACUNDO