الفهرس 
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Abstract
Given its rising prevalence in both rich and developing nations, obesity is a global health concern. One of the main causes of obesity is a high-fat diet, which has also been found to have an impact on cardiac health. Obesity is significantly associated with mortality, lipotoxic cardiomyopathy, and heart failure. The prevalence of obesity has reached alarming levels throughout the world, and mounting data points to the possibility that the nutritional status of the parents may predispose the children to lipotoxic cardiomyopathy. The most significant contributing factor to the halted fall in the death rates from cardiovascular disease seen in developed countries over the past ten years is thought to be the rising incidence of obesity. So, the current work aimed to investigate the sex-difference trans-generation impacts of maternal and/or paternal obesity and to explore some of the molecular changes induced in the cardiac tissue of male and female first generation (F1) offspring to understand the underlying mechanisms and pave the way to precision medicine for the development of potential interventions and tackle future diseases in subsequent generations.
The study was conducted on 40 adult Wistar albino rats (20 males and 20 females). Obesity was induced by feeding them obesogenic diet for 3 months. The pregnancy was induced in the females by mating with males in four combinations: healthy mother with healthy father (control parents, CP), healthy mother with obese fathers (OF), obese mothers with healthy father (OM), and obese mother with obese father (obese parents, OP). After delivery, the male and female offspring at two months were sacrificed to obtain blood samples and heart tissues. Blood samples were separated for determination of glucose homeostasis parameters, lipid profile, and cardiac function tests. The obtained cardiac tissue was washed in ice cold saline and snap frozen, part of the obtained cardiac tissue was kept in formalin for histology, second part was used for RNA isolation for determination of gene expression analysis and determination of protein contents.
In the present study, the maternal and/or paternal obesity significantly affect pregnancy outcomes and the health of the offspring, as indicated by higher neonatal weights and age-dependent increase in the body weight throughout the follow-up period (8 weeks) with the most pronounced effect observed in male offspring. The observed obesogenic behavior of the offspring was associated with cardiac abnormalities at the histological level as indicated by significantly elevated cardiac lesions scores in both female and male offspring of all obese groups especially when both parents were obese. The female offspring appeared to be more affected than males.
The histopathological abnormalities in the cardiac tissues of the female and male offspring of obese mothers and fathers were associated with significant elevation in the circulatory cardiac biomarkers including the activities of AST, CK-MB, indicating the presence of mild cardiac damage in those offspring. Also, associated with insulin resistance and disturbance of lipid profile. These abnormalities in serum lipid profile and cardiac TG contents were coincident with marked changes in the lipid metabolites in serum and cardiac tissues as indicated by significant elevation of serum and cardiac contents of ceramide and cardiolipin. The maternal and paternal obesity showed marked enhancing cardiac amyloidogenesis showed by increase expression of APP and induction of oxidative stress which contribute to mitochondrial dysfunction in both male and female offspring.
from this study, we can conclude that:
1. Maternal and paternal obesity differentially affect the lipid profile in the offspring but have similar reprogramming effect on the cardiac system in a sex-dependent manner.
2. The maternal and paternal obesity result in long-term consequences on cardiac tissue of females and males F1-offspring through impairing mitochondrial biogenesis, enhancing cardiac amyloidogenesis and elevated oxidative stress.
3. Our findings demonstrate the urgent need for methods to prevent obesity in women of reproductive age and the necessity of determining the cardiovascular risk of the children of obese mothers.
4. The exact mechanisms underlying the effects of maternal and paternal obesity on the cardiovascular system of their offspring are still not fully understood, however, it is thought that epigenetic changes may play a role.
5. The crosstalk between genetic events together with sex hormones and the epigenetic changes in the sperm and ova, which may contribute to sex-difference response to the maternal and/or paternal obesity, needs further investigations.