Abstract
Breast milk cholesterol content may imply to affect short- and long-term cholesterol homeostasis in the offspring. However, mechanisms of regulating milk cholesterol concentration are only partly understood. We used different mouse models to assess the impact of high cholesterol diet (HC)- or genetically-induced hypercholesterolaemia on milk cholesterol content. At day 14 postpartum we determined milk, plasma and tissue lipids in wild type (WT), LDL receptor knockout (Ldlr−/−), and ATP-binding cassette transporter G8 knockout (Abcg8−/−) mice fed either low- or 0.5% HC diet. In chow-fed mice, plasma cholesterol was higher in Ldlr−/− dams compared to WT. HC-feeding increased plasma cholesterol in all three models compared to chow diet. Despite the up to 5-fold change in plasma cholesterol concentration, the genetic and dietary conditions did not affect milk cholesterol levels. To detect possible compensatory changes, we quantified de novo cholesterol synthesis in mammary gland and liver, which was strongly reduced in the various hypercholesterolaemic conditions. Together, these data suggest that milk cholesterol concentration in mice is not affected by conditions of maternal hypercholesterolaemia and is maintained at stable levels via ABCG8- and LDLR-independent mechanisms. The robustness of milk cholesterol levels might indicate an important physiological function of cholesterol supply to the offspring.
Highlights
Breast milk contains high levels of cholesterol (0.23–0.39 mmol/L) in contrast to most infant formulas (0–0.10 mmol/L)[1,2,3]
The size of the effect reached maximum in the Ldlr−/− mice (4.8-fold change, p < 0.01) followed by Abcg8−/− (2-fold change, p < 0.05) and wild-type (1.5-fold change, p < 0.05)
Hepatic cholesterol concentration corresponded with the differences in the plasma cholesterol levels: similar levels in wild-type and Abcg[8] knockout mice and 0.6-fold higher in LDLR-deficient mice (p < 0.01)
Summary
Breast milk contains high levels of cholesterol (0.23–0.39 mmol/L) in contrast to most infant formulas (0–0.10 mmol/L)[1,2,3]. It remains unclear to what extent maternal hypercholesterolaemia, either caused by genetic or dietary factors, impacts cholesterol transport across the mammary gland and affects cholesterol concentration in milk with possible effects in the offspring. The LDL-receptor is the dominant transport protein involved in the uptake of apoB100-containing lipoproteins from the plasma[22], and highly expressed in murine mammary gland[21]. We assessed the potential relevance of cholesterol secretion into milk via the ABCG8 transporter and via mammary gland uptake of cholesterol via the LDL receptor. To assess possible variation in the origin of milk cholesterol in the different models of hypercholesterolaemia, we measured de novo cholesterol synthesis in the liver and mammary gland, using deuterated water methodology
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