Banca de DEFESA: SUELEN GUEDES ZECA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : SUELEN GUEDES ZECA
DATE: 18/09/2020
TIME: 08:00
LOCAL: Webconferência
TITLE:

Studying inter- and transgenerational transmission of metabolic, behavioral, and heart phenotypes on mice offspring for two consecutive generations

KEY WORDS:

echocardiogram, epigenetic, maternal, and paternal obesity

PAGES: 113
BIG AREA: Ciências Biológicas
AREA: Fisiologia
SUBÁREA: Fisiologia Geral
SUMMARY:

Evidence has shown the effects of maternal obesity (MO) at the transmission of metabolic, behavioral, and cardiovascular dysfunction on the offspring, possible due to epigenetic changes on germline cells from one or both progenitors. In Drosophilas, paternal obesity (PO) leads to obesity and metabolic impairment through epigenetic sperm changes, but not much is known on mammals. This project aimed to understand if MO and PO shift metabolism, behavior and cardiac function in basal conditions, for two consecutive generations. Female and male C57BL/6J mice were fed normal chow (NC, 6% fat) or high-fat diets (HF45, 45% fat and HF60, 60% fat) ad libitum from 4 to 10 weeks old, when body composition (NMR), glucose metabolism (GTT) and behavioral (open field, OF) analysis were performed. After the testing, groups NC, HF45, and HF60 labeled F0 generation, were mated with NC animals in order to obtain F1. To increase the programming influence, the intercross of the F1 animals within their groups obtained the F2 generation. Except for F0, all mice were kept under the NC diet throughout the experiment. The experiments NMR and GTT (6, 10, 15, and 25 weeks old), OF (13 weeks old) and echocardiogram (25 weeks old) were performed on both F1 and F2 offspring. We observed that male and female F0-HF45 and F0-HF60 had a higher body weight and adiposity. F0-HF60 females, F0-HF45 and F0- HF60 males had impaired glucose metabolism. No significant changes were noted on the due percentage or number of pups per litter; however, F0-HF60 females had lower pup survival percentages after weaning. Regarding maternal obesity, only F1-MHF45 males showed increased body weight and adiposity. F1-MHF45 e F1-MHF60 male had also impaired glucose metabolism. Paradoxically, F2-MHF45 males had a lower body weight. The cardiac function was normal on F1-MHF45 and F1-MHF60 males, but a substantial decrease in the ejection fraction with increased left-ventricle (LF) end-systolic volume was observed in F2- MHF45 males. The only significant change observed on F1-MHF45 females were an increased center timer during the OF test. Regarding paternal obesity, we saw an increased body weight and adiposity on F1-PHF45 offspring (both sexes) and F1-PHF60 males. Paradoxically, F2-PHF45 had a decreased body weight, and female F2-PHF45 had lower adiposity, with no changes in glucose metabolism on both F1 and F2. Behavioral analysis showed conflicting results on rearing time between F1- and F2-PHF45 males, and increased center time on F1-PHF45 females. The heart function was normal on F1, but a substantially reduced ejection fraction and increased left-ventricle (LF) end-systolic volume were observed in F2-MHF45 offspring. In summary, the male lineage was more affected by maternal obesity, while most of the changes were observed regardless of the sex on the paternal obesity model. We can conclude that while the cardiac impairment through MO occurs only on the male lineage, on the PO, this phenomenon happens in a sex- and obesity-independent manner, showing how relevant it is to search for epigenetic markers that could maintain the phenotype on the offspring.

BANKING MEMBERS:
Externa à Instituição - NATÁLIA GALITO ROCHA AYRES - UFF
Externa à Instituição - PATRÍCIA CRISTINA LISBOA DA SILVA - UERJ
Interno - 3000663 - DAVID DO CARMO MALVAR
Interno - 1519567 - FABIO FAGUNDES DA ROCHA
Presidente - 2479104 - NORMA APARECIDA DOS SANTOS ALMEIDA