Adipose tissue as a key organ in the pathogenesis of metabolic syndrome in adult rats born after an intra-uterine growth restriction

Details

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Serval ID
serval:BIB_8FCCC2B54819
Type
A Master's thesis.
Publication sub-type
Master (thesis) (master)
Collection
Publications
Institution
Title
Adipose tissue as a key organ in the pathogenesis of metabolic syndrome in adult rats born after an intra-uterine growth restriction
Author(s)
COPPOLA H.
Director(s)
YZYDORCZYK C.
Institution details
Université de Lausanne, Faculté de biologie et médecine
Publication state
Accepted
Issued date
2021
Language
english
Number of pages
33
Abstract
Introduction
Metabolic syndrome (MetS) is one of the world’s non-communicable diseases (NCDs) and consists of the association of arterial hypertension, visceral obesity, type II diabetes, hypercholesterolemia, hyperlipidaemia, and non-alcoholic fatty liver disease (NAFLD). People subject to MetS are at a higher risk of developing cardiovascular diseases and cancers during their lifetime.
People with MetS often can exhibit an unfavourable lifestyle consisting of lack of physical exercise and/or an unhealthy diet, but children born after an intrauterine growth restriction (IUGR) also seem to be at a higher risk for developing this NCD. The concept of “Developmental Origins of Health and Diseases” (DOHaD) explores the relation between these two pathologies.
Adipose tissue (AT), with its immune and endocrine functions, could play an important role in the pathogenesis of MetS in subjects with IUGR. However, the cellular and molecular mechanisms are not yet fully understood. The objective of this study is to identify the structural and functional alterations of AT in a IUGR male rat model.
Methods
For this project, a rat model was used, in which pregnant rats were fed during their full gestation period with either a control regime (23% casein) or a low protein regime (9% casein) which induced an IUGR in the offspring. The postnatal diet of the newborns was then the same for all. The AT of male and female offspring was studied at 6 months of age (preliminary data).
Hyperplasia of the AT was observed through histological staining, highlighting Ki67 expression. Adipogenesis was evaluated using peroxisome proliferator-activated receptor gamma (PPAR-γ) (western blot) and zinc finger protein 423 (ZFP423) (RT-qPCR). Inflammation was studied by using IL1-β (western blot), IL-6, TNF- α, ITGAM, ITGAX, CD36, CD68 and MCP-1 (RT-qPCR). Observation of superoxide anions (hydroethidine fluorescence) was used to evaluate the presence of oxidative stress (OS), and protein quantification of superoxide dismutase (SOD) and catalase (western blot) were utilised for evaluation of antioxidant defences. Finally, senescence was evaluated with p21, p16 and sirtuin-1 (SIRT-1) expression (western blot).
All parameters were presented as mean +/- their standard error of mean (SEM) and were compared using the Mann-Whitney U test. The level of significance was set at p < 0.05.
Results
In the histological samples, an increase in Ki67 expression in the 6-month-old IUGR males was observed. The IUGR males also presented a significant increase in PPAR-γ and ZFP423 expression, as well as in IL1-β, IL-6, TNF-α, ITGAM, ITGAX and CD68, but no differences in CD36 or MCP-1. They also presented a significant increase of superoxide anions, catalase, and SOD, and finally a significantly increased expression of SIRT-1, p-16, and p-21.
Discussion
The male IUGR group presents structural and functional modifications in their AT compared to the CTRL model. These changes are induced by IUGR and are characterized by increased levels of hyperplasia, inflammation, OS, and senescence in the AT, and may be factors that favour the development of MetS in later life.
Keywords
developmental origins of health and disease, adipose tissue, intra-uterine growth restriction, metabolic syndrome, inflammation
Create date
12/09/2022 10:41
Last modification date
11/01/2023 6:53
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