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Peroxisome proliferator‐activated receptor α is not the exclusive mediator of the effects of dietary cyclic FA in mice
Author(s) -
Bretillon Lionel,
Alexson Stefan E. H.,
Joffre Florent,
Pasquis Bruno,
Sébédio JeanLouis
Publication year - 2003
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-003-1149-y
Subject(s) - peroxisome , peroxisome proliferator activated receptor , mediator , endocrinology , medicine , receptor , lipid metabolism , chemistry , biology , biochemistry
Cyclic FA monomers (CFAM) formed during heating of α‐linolenic acid have been reported to interfere in hepatic metabolism in a putatively peroxisome proliferator‐activated receptor α (PPARα)‐dependent manner. In the present work, CFAM (0.5% of the diet) were administered for 3 wk to wild‐type and PPARα‐null mice of both genders to elucidate the role of PPARα in mediating the effects of CFAM on the activity of acyl‐CoA oxidase (ACO) and ω‐laurate hydroxylase (CYP4A), the regulation of which is known to be dependent on the PPARα. Dietary CFAM enhanced CYP4A activity threefold in male and female wild‐type mice. This effect was abolished in PPARα‐null mice. A twofold induction of ACO activity was found in wild‐type female mice fed CFAM; however, no effect was seen in males. In wild‐type animals, (ω‐1)‐laurate hydroxylase (CYP2E1) activity, the expression of which has not been shown to be PPARα dependent, was not affected by the CFAM diet. In contrast, stearoyl‐CoA desaturase activity was reduced in wild‐type mice. CFAM feeding reduced the activities of ACO, CYP2E1, and stearoyl‐CoA desaturase and caused accumulation of lipids in the livers of female PPARα‐null mice. These data show that CFAM apparently activate gene expression via the PPARα and have profound effects on lipid homeostasis, exacerbating the disturbances preexisting in mice lacking functional PPARα. Although the data emphasize the importance of PPARα in the metabolism of the CFAM, these results show that PPARα is not the exclusive mediator of the effects of CFAM in lipid metabolism in mice.