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Proposed metabolic pathways involved in fatty acid and cholesterol accumulation in the livers of n-3 PUFA depleted mice.

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posted on 2011-08-10, 02:13 authored by Barbara D. Pachikian, Ahmed Essaghir, Jean-Baptiste Demoulin, Audrey M. Neyrinck, Emilie Catry, Fabienne C. De Backer, Nicolas Dejeans, Evelyne M. Dewulf, Florence M. Sohet, Laurence Portois, Louise Deldicque, Olivier Molendi-Coste, Isabelle A. Leclercq, Marc Francaux, Yvon A. Carpentier, Fabienne Foufelle, Giulio G. Muccioli, Patrice D. Cani, Nathalie M. Delzenne

The reduction of fatty acid oxidation and the induction of lipogenesis both contribute to the accumulation of lipids in the livers of n-3 PUFA-depleted mice. The reduced fatty acid degradation could result from the inhibition of the PPARα pathway. De novo lipogenesis is promoted through SREBP-1c activation. Data suggest that SREBP-1c activation could result from both increased hepatic 2-AG content and LXR activation. The lower n-3 PUFA content in hepatic phospholipids can lead to higher 2-AG production, which could therefore stimulate CB1 and then SREBP-1c expression. Both hepatic n-3 PUFA depletion and higher cholesterol content contribute to LXR activation. Increased SREBP-2 activation, occurring by an unknown mechanism, could play a role in the increased cholesterol synthesis observed in the n-3 PUFA-depleted livers.