title: 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.
abstract: 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.
  
  
  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 [(3)H]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 [(3)H]cholesterol efflux to plasma and HDL-derived [(3)H]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 [(3)H]cholesterol excretion was totally blunted in ABCG5/G8-deficient mice.
  
  
  CONCLUSIONS
  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.
authors: Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain. jescola@santpau.cat
authors: Joan Carles
authors: JC
authors: Escolà-Gil
authors: Gemma
authors: G
authors: Llaverias
authors: Josep
authors: J
authors: Julve
authors: Matti
authors: M
authors: Jauhiainen
authors: Jesús
authors: J
authors: Méndez-González
authors: Francisco
authors: F
authors: Blanco-Vaca
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000378:metabolism*; D004041:Dietary Fats / Q000494:pharmacology; D005243:Feces; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000172:deficiency / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C462600:ABCG5 protein, mouse; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D004041:Dietary Fats; D008074:Lipoproteins; D002784:Cholesterol