الفهرس 
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Abstract
About one third of the worldwide population is now suffering from overweight or obesity. It is described by excess fat in the body, which rises the risk of emerging lasting diseases such as diabetes, heart disease, and certain kinds of cancer. The effects of being fatty are not only person’s health but also spread to trans-generation problems. Children of parents suffering from obesity can be obese also due to genetic and environmental reasons. This vicious cycle of obesity and related health problems can cause long-term problems for peoples and society.
In the last decades, evidences from human and animal study says that suffering from parental obesity in the time of pregnancy can have an adverse effects on health of the kids through development programming. This makes significant influences to the universal incidence of obesity and linked metabolic problems like diabetes, cardiovascular disease, and liver diseases. Moms and dads suffering from obesity is a risk factor for developing non-alcohol fatty liver disease (NAFLD) in their children, however, little is known about the sex-dependent response to moms and/or dads suffering from fatness. Given that the frequency of fatty women and men of reproductive age is growing extremely, it is crucial to better define the changes in children and its consequences. Also, the molecular changes that may occur in the offspring of parents suffering from obesity need in-depth analysis to understand the molecular mechanism(s) of the trans-generation effects of fatness for good management and controlling of fatness. So, the present study aimed to explore sex-difference trans-generation effects of maternal and/or paternal suffering from obesity, and to find some of the molecular changes induced in the liver cells tissues of female and males first generational (F1) offspring to understand the underlying mechanisms and pave the way to precision medicine to develop potential interventions and tackle future diseases in following generations.
This study was conducted on 40 albino rats. Rats were grouped into 4 groups :(group I): included mating between 5 healthy female rats and 5 healthy male rats that were maintained under normal diet.(group II): included mating between 5 male rats that were fed on HFD for three months and 5 healthy female rats fed on normal diet. (group III): included mating between 5 female rats that were fed on HFD for three months and 5 healthy male rats fed on normal diet. (group IV): included mating between 5 male rats and 5 female rats both fed on HFD for three months. Pregnancy was induced in all groups overnight. The next day was considered as day 0 of pregnancy (gestational Day 0). After two months of delivery the rats were dissected out to obtain blood samples and liver tissues. Blood samples were be separated for determination of glucose homeostasis parameters, lipid profile, and liver function tests. The obtained liver tissue was washed in ice cold saline and snap frozen, part of the obtained liver tissue was kept in formalin for histology. Part of the liver tissue was dissected out for hepatic RNA isolation for determination of: mtDNA-CN, and gene expression analysis.
The results of the present study clearly indicated that maternal and/or paternal obesity significantly affect the pregnancy outcomes and the health of the offspring as indicated by higher birth weights and age-dependent increase in the body weight throughout the follow-up period (8 weeks) especially the male offspring. The observed obesogenic behavior of the offspring was associated with hepatic manifestations of NAFLD as indicated by significant increase in the hepatic steatosis in both female and male offspring of all obese groups especially when the mother or both parents were obese. The histopathological abnormalities in the liver of the female and male offspring of obese mothers and fathers were associated with significant elevation in the circulatory liver biomarkers including the activities of AST and ALT enzymes, and the levels of total and direct bilirubin. Also, the female and male offspring of obese mother and/or father showed significant elevation in fasting blood sugar, serum insulin, and insulin resistance index (HOMA-IR) compared with the control offspring indicating a state of insulin resistance. The impaired glucose metabolism in the offspring is associated with significant changes in the serum lipid profile. These metabolic abnormalities were associated with imbalance in oxidant-antioxidant status and inflammation together with cytoplasmic vacuolation, necrosis and mononuclear inflammatory cells infiltrations in hepatocytes. Upregulation of amyloid precursor protein gene, decrease in mtDNA-CN, alteration in mitochondrial biogenesis genes (PGC-1α, NRF1, UCP2) expression, up regulation of lipogenic gene (SREBP-1c) and down regulation of (SCD1) gene were also reported in liver tissue of offspring of all studied groups. Results were more prominent when both parents were obese compared with only one obese parent.