title: Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids.
abstract: BACKGROUND
  Milk phospholipids (PLs) reduce liver lipid levels when given as a dietary supplement to mice fed a high-fat diet. We have speculated that this might be due to reduced intestinal cholesterol uptake.
  
  
  METHODS
  Mice were given a high-fat diet for 3 or 5 weeks that had no added PL or that were supplemented with 1.2% by wt PL from cow's milk. Two milk PL preparations were investigated: a) a PL-rich dairy milk extract (PLRDME), and b) a commercially-available milk PL concentrate (PC-700). Intestinal cholesterol uptake was assessed by measuring fecal and hepatic radioactivity after intragastric administration of [14C]cholesterol and [3H]sitostanol. Fecal and hepatic lipids were measured enzymatically and by ESI-MS/MS.
  
  
  RESULTS
  Both PL preparations led to significant decreases in total liver cholesterol and triglyceride (-20% to -60%, P < 0.05). Hepatic accumulation of intragastrically-administered [14C]cholesterol was significantly less (-30% to -60%, P < 0.05) and fecal excretion of [14C]cholesterol and unlabeled cholesterol was significantly higher in PL-supplemented mice (+15% to +30%, P < 0.05). Liver cholesterol and triglyceride levels were positively correlated with hepatic accumulation of intragastrically-administered [14C]cholesterol (P < 0.001) and negatively correlated with fecal excretion of [14C]cholesterol (P < 0.05). Increased PL and ceramide levels in the diet of mice supplemented with milk PL were associated with significantly higher levels of fecal PL and ceramide excretion, but reduced levels of hepatic PL and ceramide, specifically, phosphatidylcholine (-21%, P < 0.05) and monohexosylceramide (-33%, P < 0.01).
  
  
  CONCLUSIONS
  These results indicate that milk PL extracts reduce hepatic accumulation of intestinal cholesterol and increase fecal cholesterol excretion when given to mice fed a high-fat diet.
authors.affiliation: Nutrition and Metabolism Group, Heart Research Institute, Sydney, Australia. cohnj@hri.org.au.
authors.forename: Alvin
authors.initials: A
authors.lastname: Kamili
authors.forename: Elaine
authors.initials: E
authors.lastname: Wat
authors.forename: Rosanna Ws
authors.initials: RW
authors.lastname: Chung
authors.forename: Sally
authors.initials: S
authors.lastname: Tandy
authors.forename: Jacquelyn M
authors.initials: JM
authors.lastname: Weir
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Meikle
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Cohn