الفهرس 
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Abstract
Obesity stands as a major focal point of public health, being classified as the fifth leading cause of death on a global scale. Obesity affects every country, and certain developing countries have showed the highest increases in obesity rates over the past decade. Not a single country has observed a decrease in obesity prevalence among their entire population, and none are making progress towards achieving the World Health Organization’s goal of preventing any increase in obesity levels compared to 2010 by the year 2025. The health impacts of obesity are not limited to the obese individuals but also extend to their offspring (Intergenerational or trans-generational effects) as the children of obese mother and/or father are more likely to become obese themselves due to genetic and environmental factors which generating a vicious cycle of obesity and related health problems with long-term consequences for individuals and society. A part from the genetic factors, human and animal studies confirm that parental obesity pre-conceptional/peri-conceptional can have adverse effects on the health of the offspring by developmental reprogramming or epigenetic changes (changes in gene expression) not genetic changes that has been found to increase the risks of obesity and related reproductive and metabolic disorders in offspring, independent of the genetic makeup. 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 two distinct types of adipose tissues (white and brown) of the first-generation (F1) male and female offspring for proper understand the underlying mechanisms and pave the way for the development of potential interventions and tackle future diseases in subsequent generations.
The study involved a total of 40 Wistar albino rats, divided equally into 20 males and 20 females. To induce obesity, the rats were fed an obesogenic diet for a duration of three months. Pregnancy was induced in the female rats through mating, resulting in four combinations: healthy mothers with healthy fathers (control parents, CP), healthy mothers with obese fathers (OF), obese mothers with healthy fathers (OM), and obese parents consisting of both obese mother and father (OP). After the offspring were born, both male and female offspring were sacrificed at the age of two months to collect blood samples and heart tissues for analysis. Blood samples were separated for determination of glucose homeostasis parameters, lipid profile, and cardiac function tests. The obtained WAT& BAT \ were washed in ice cold saline and snap frozen, part of the obtained WAT& BAT
was kept in formalin for histology, second part was used for RNA isolation for determination of gene expression analysis and determination of protein contents.
The current study’s findings clearly show that maternal and/or paternal obesity have a significant impact on pregnancy outcomes and offspring health, as evidenced by higher birth weights and age-dependent increases in body weights throughout the 8-week follow-up period, and then higher adult weights of female and male offspring of obese mothers and obese parents (especially the male offspring).
The observed obesogenic behavior of the offspring was associated with abnormalities in WAT and BAT at the histological level as indicated by enlarged irregular outlined adipocyte, inflammatory foci with inflammatory cells infiltration and crown-like structures of WAT. Also, BAT showed enlargement and marked increased adipocytes diameter which may indicate the transformation into storage WAT-like tissues. These effects are more prominent in female offspring of obese mothers or obese parents with male offspring showed mild abnormalities especially those offspring of obese fathers. These histopathological abnormalities in both types of adipose tissues of the female and male offspring of obese mothers were associated with significant alterations in the pathway of mitochondrial biogenesis.
from the previous discussion, we can conclude that:
1. The results of this study highlight the essential role of intergenerational effects on the obesity pandemic around the world and the pressing necessity for implementing strategies that target the prevention of obesity in both men and women of reproductive age, as well as the importance of evaluating the health outcomes of children born to obese mothers.
2. The mechanisms underlying the effects of maternal and paternal obesity on WAT and BAT of their offspring are not fully understood.
3. The induced inflammation and impaired mitochondrial biogenesis in WAT and BAT results in WAT expansion and impaired BAT functions resulting obesogenic behavior of the offspring.
4. 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 or paternal obesity needs further investigations.