| First Author | Desmarais F | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Cell Biol Lipids | Volume | 1864 |
| Issue | 4 | Pages | 522-531 |
| PubMed ID | 30630053 | Mgi Jnum | J:270743 |
| Mgi Id | MGI:6277616 | Doi | 10.1016/j.bbalip.2019.01.001 |
| Citation | Desmarais F, et al. (2019) Apolipoprotein D overexpression alters hepatic prostaglandin and omega fatty acid metabolism during the development of a non-inflammatory hepatic steatosis. Biochim Biophys Acta Mol Cell Biol Lipids 1864(4):522-531 |
| abstractText | 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 PPARgamma 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 6months with a transient overexpression of L-PGDS and concomitant overproduction of 15d-PGJ2, a PPARgamma agonist. Hepatic lipid accumulation was detectable as soon as 9months. Inflammatory polarization balance varied in time, with a robust anti-inflammatory profile at 6months 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. PPARgamma 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. |
