Effets physiologiques et signature métabolomique de peptides de saumon et d'acides gras oméga-3 dans un modèle murin du syndrome métabolique
|Abstract:||The main objective of this thesis was to evaluate the metabolic and mechanistic effects of a low-molecular-weight salmon peptide fraction (SPF) combined or not with omega-3-rich fish oil (FO) in the context of diet-induced obesity (DIO) in a murine model of the metabolic syndrome (MetS), the LDL-/-/ApoB100/100 mouse. In the first study, we have shown that mice fed the SPF alone or in combination with FO (SPF+FO) were more glucose tolerant and had marked improvements in their plasma lipid profile, adipose tissue inflammation and hepatic insulin signaling pathway. These effects were associated with a small reduction in body weight, liver weight and energy efficiency. These in vivo effects were then validated in 3 cell lines. Secondly, we validated once again the beneficial impact of SPF on glucose tolerance after 3 months of diet. We aimed to explore its mechanisms of action by doing an extensive assessment of the acylcarnitine (AC) plasma metabolome and the hepatic gene expression of the mice. We found that adiponectin levels and many hepatic genes involved in inflammation, in glucose and lipid homeostasis and in mitochondrial and peroxisomal β-oxidation were altered with SPF and FO. The AC profile was modified upon dietary treatment with FO and SPF, with significant changes in short-, medium- and long-chain AC. Thirdly, we validated the beneficial effects of SPF on glucose tolerance over a 6- month period, and decided to concentrate on the metabolomic profile of plasma amino acids (AA). We aimed to understand the important alterations that occured after 6-months on diet in the SPF-fed animals. Then we also looked at changes in the proteins and enzymes regulating branched-chain amino acids (BCAA) catabolism in liver, skeletal muscle and epidydimal adipose tissue by Western blotting. The metabolomic analyses of plasma obtained after 3 months of diet in our other cohort of mice gave us the opportunity to evaluate the association between the AA signature and the physiological effects of SPF. These studies show the potential of SPF combined or not with FO as a nutraceutical for the prevention of obesity-related complications, such as glucose intolerance, low-grade inflammation and dyslipidemia.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||9 November 2019|
|Collection:||Thèses et mémoires|
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