Los ácidos grasos poliinsaturados disminuyen la expresión in vitro de la proteína NPC1L1, clave en la absorción intestinal de colesterol

Identificador:  imarina:5608122

Handle: https://hdl.handle.net/20.500.11797/imarina5608122

Autors:  Álvaro A; Rosales R; Masana L; Vallvé J

Resum:
Background. Several transporter proteins regulate intestinal cholesterol absorption. Of these proteins, NPC1L1 plays a major role to this process. Fatty acids (FA) modulate cholesterol absorption by a mechanism that remains unknown. Objectives. To evaluate the effect of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids on the expression of NPC1L1 in human enterocytes in vitro and to study the role of the nuclear receptors PPARγ, PPARδ, LXR and RXR. Methods. Caco-2/TC-7 enterocytes were incubated for 24 h with non-cytotoxic concentrations (50, 100, 200 and 300 μM) of the different FA. NPC1L1 gene expression was analyzed by quantitative rtPCR and the protein present in enterocyte membranes was analyzed by western blot. Results. NPC1L1 mRNA levels were reduced 35 to 58% by the n-3 PUFA, EPA and DHA (p < 0.05). LA (n-6), PA, and OA did not affect NPC1L1 mRNA expression. ABCA1 mRNA levels were reduced 44 to 70% by n-6 AA and 43 to 55% by n-3 EPA (p < 0.05). LXR and LXR+RXR agonists decreased NPC1L1 mRNA expression by 28 and 57%, respectively (p < 0.05). A concentration of 200 μM of EPA and DHA decreased NPC1L1 protein expression in enterocyte membranes by 58% and 59%, respectively. Conclusions. We have demonstrated that the PUFAs n-3 EPA and DHA down-regulate NPC1L1 mRNA expression in vitro. In addition, PUFA also down-regulate NPC1L1 protein expression in enterocyte membranes. LXR and RXR activation induced a similar repression effect. The lipid lowering effect of n-3 PUFA could be mediated in part by their action at the NPC1L1 gene level.