Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis

Desmarais, Frederik; Bergeron, Karl-F.; Rassart, Eric et Mounier, Catherine (2019). « Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis ». Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids.

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Résumé

Apolipoprotein D (ApoD) is a secreted lipocalin associated with neuroprotection and lipid metabolism. Overexpression of ApoD in mouse neural tissue induces the development of a non-inflammatory hepatic steatosis in 12-month-old transgenic animals. Previous data indicates that accumulation of arachidonic acid, ApoD's preferential ligand, and overactivation of PPARγ are likely the driving forces in the development of the pathology. However, the lack of inflammation under those conditions is surprising. Hence, we further investigated the apparent repression of inflammation during hepatic steatosis development in aging transgenic animals. The earliest modulation of lipid metabolism and inflammation occurred at 6 months with a transient overexpression of L-PGDS and concomitant overproduction of 15d-PGJ2, a PPARγ agonist. Hepatic lipid accumulation was detectable as soon as 9 months. Inflammatory polarization balance varied in time, with a robust anti-inflammatory profile at 6 months coinciding with 15d-PGJ2 overproduction. Omega-3 and omega-6 fatty acids were preferentially stored in the liver of 12-month-old transgenic mice and resulted in a higher omega-3/omega-6 ratio compared to wild type mice of the same age. Thus, inflammation seems to be controlled by several mechanisms in the liver of transgenic mice: first by an increase in 15d-PGJ2 production and later by a beneficial omega-3/omega-6 ratio. PPARγ seems to play important roles in these processes. The accumulation of several omega fatty acids species in the transgenic mouse liver suggests that ApoD might bind to a broader range of fatty acids than previously thought.

Type: Article de revue scientifique
Mots-clés ou Sujets: Apolipoprotein D; Hepatic steatosis; Omega-3 fatty acid; Omega-6 fatty acid; Peroxisome proliferator-activated receptor γ; Prostaglandin 15d-PGJ(2)
Unité d'appartenance: Faculté des sciences > Département des sciences biologiques
Déposé par: delegation Karl-Frédérik Bergeron
Date de dépôt: 01 févr. 2019 09:36
Dernière modification: 01 févr. 2019 09:36
Adresse URL : http://archipel.uqam.ca/id/eprint/12162

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