The cholesterol content of western diets plays a major role in the paradoxical increase in high-density lipoprotein cholesterol and upregulates the macrophage reverse cholesterol transport pathway
Por:
Escolà-Gil J.C., Llaverias G., Julve J., Jauhiainen M., Méndez-González J., Blanco-Vaca F.
Publicada:
1 ene 2011
Resumen:
Objective-: A high-saturated fatty acid-and cholesterol-containing (HFHC) diet is considered to be a major risk factor for cardiovascular disease. The present study aimed to determine the effects of this Western-type diet on high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) from macrophages to feces. Methods and Results-: Experiments were carried out in mice fed a low-fat, low-cholesterol diet, an HFHC diet, or an HFHC diet without added cholesterol (high-saturated fatty acid and low-cholesterol [HFLC]). The HFHC diet caused a significant increase in plasma cholesterol, HDL cholesterol, and liver cholesterol and enhanced macrophage-derived [ 3H]cholesterol flux to feces by 3-to 4-fold. These effects were greatly reduced in mice fed the HFLC diet. This HFHC diet-mediated induction of RCT was sex independent and was not associated with obesity or insulin resistance. The HFHC diet caused 1.4-and 3-fold increases in [H]cholesterol efflux to plasma and HDL-derived [ 3H]tracer fecal excretion, respectively. Unlike a low-fat, low-cholesterol and HFLC diets, the HFHC diet increased liver ABCG5/G8 expression. The effect of the HFHC diet on fecal macrophage-derived [ 3H]cholesterol excretion was totally blunted in ABCG5/G8-deficient mice. Conclusion-: Despite its deleterious effects on atherosclerosis, the HFHC diet promoted a sustained compensatory macrophage-to-feces RCT. Our data provide direct evidence of the crucial role of dietary cholesterol signaling through liver ABCG5/G8 upregulation in the HFHC diet-mediated induction of macrophage-specific RCT. © 2011 American Heart Association. All rights reserved.
Filiaciones:
Escolà-Gil J.C.:
Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain
Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain
Llaverias G.:
Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain
Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain
Julve J.:
Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain
Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain
Jauhiainen M.:
National Institute for Health and Welfare, FIMM Institute for Molecular Medicine Finland, Biomedicum, Helsinki, Finland
Méndez-González J.:
Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain
Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
Blanco-Vaca F.:
Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain
Centro de Investigación en Red de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain
Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain
Hospital de la Santa Creu i Sant Pau, Servei de Bioquímica, C/Antoni M Claret 167, 08025 Barcelona, Spain
Bronze, All Open Access; Bronze
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