Hepatic accumulation of intestinal cholesterol is decreased and fecal cholesterol excretion is increased in mice fed a high-fat diet supplemented with milk phospholipids

Alvin Kamili,Sally Tandy,Jacquelyn M Weir,Rosanna Ws Chung,Elaine Wat,Peter J Meikle,Jeffrey S Cohn

doi:10.1186/1743-7075-7-90

Abstract

BackgroundMilk 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.MethodsMice 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.ResultsBoth 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).ConclusionThese 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.

Highlights

Milk phospholipids (PLs) reduce liver lipid levels when given as a dietary supplement to mice fed a high-fat diet
Our laboratory has been investigating the lipid-lowering properties of PL from different sources [2,3,4], and we have shown that a PL-rich dairy milk extract (PLRDME), containing predominantly phosphatidylcholine (PC), sphingomyelin (SM) and
Metabolic parameters were assessed after 3 or 5 weeks in mice fed the HF diet alone and in those given the HF diet supplemented with PLRDME (Table 1)

Summary

Introduction

Milk phospholipids (PLs) reduce liver lipid levels when given as a dietary supplement to mice fed a high-fat diet. The ability of dietary PL to lower plasma and liver lipid levels in mice fed a high-fat diet is unlikely to be due to their polyunsaturated fatty acid content This is supported by recent work from our laboratory showing that hydrogenated egg and soy PC, containing only saturated fatty acids (i.e., C16:0 and C18:0), lower liver lipids to a greater extent than non-hydrogenated PC preparations, containing 20% and 70% polyunsaturated fatty acids respectively (i.e., C18:2 and C18:3) [4]. Uptake and esterification of cholesterol by human intestinal Caco-2 cells is reduced to a greater extent by milk SM or by dipalmitoyl PC (containing saturated fatty acids) than by egg yolk PC, and in mice, milk SM or dipalmitoyl PC, but not egg PC, has been shown to cause a dose-dependent decrease in cholesterol absorption [8]

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