Modulation de l'expression de Med15 au foie dans le vieillissement et l'obésité

Authors: Gonthier, Kevin
Advisor: Picard, Frédéric
Abstract: In the nematode Caenorhabditis elegans (C. elegans), the mdt-15 cofactor, orthologous to the mammalian Med15, is essential for lipid homeostasis. Furthermore, pharmacological inhibition of the interaction between Med15 and Sterol Regulatory Element Binding Protein (SREBP) transcription factor improves the lipid profile in obese mice. The liver, important organ of energy metabolism, may undergo disorders during aging and in obesity. Modulation of Med15 hepatic levels under these two conditions is however unknown. This study aimed therefore to evaluate hepatic Med15 expression in several aging and obesity models. The aging models were C57Black/6 Jackson (B6) mice, Sprague-Dawley (SD) rats and Lou rats (a successful aging model) in different age groups and under low-fat diet (LFD). MED15 was also measured in human liver from 3 groups of obese young, middle-aged and old patients. In order to dissociate the effects of aging from those of obesity, Med15 expression was measured in 4 months old ob/ob or db/db mice under LFD and B6 mice under high-fat diet (HFD). Med15 expression was decreased in old B6 mice and SD rats but remained stable in old Lou rats and elderly patients. Med15 levels were diminished in ob/ob and db/db mice. However, Med15 protein levels were increased in mice under HFD. The general conclusion, drawn from links established between the results presented here and the literature, is that Med15 expression would be beneficial in a healthy organism but its decrease would curb the metabolic disorders associated with aging and obesity. In vitro and in vivo studies on the impacts of the variations observed in this study would allow for the Med15 characterization as a key metabolic modulator in mammals.
Document Type: Mémoire de maîtrise
Issue Date: 2019
Open Access Date: 9 February 2019
Grantor: Université Laval
Collection:Thèses et mémoires

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