Milk cholesterol concentration in mice is not affected by high cholesterol diet- or genetically-induced hypercholesterolaemia

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.

Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth

“…Despite unaltered TG in fetuses and the placentas, TG concentrations were drastically increased in the livers of 2-day-old Lal-/- offspring. This shift in hepatic lipid accumulation could be due to dietary changes, as mouse milk contains a large amount of fat and is essential for pup survival and development, being the first and only source of nutrition directly after birth [ 44 , 45 , 46 ]. In contrast to the liver, the intestine did not appear to be affected by Lal deficiency 2 days and 2 weeks postpartum.…”

Characterization of milk oligosaccharide and sialic acid content and their influence on brain sialic acid in a lean mouse model for gestational diabetes

“…(1IU, Synthocinon®, Sigma-Tau Industrie Farmaceutische Riunite). Dams were milked in a random order using a modified human electric breast pump (Calypso, Ardo Medical AG, Unterägeri, Switzerland) for up to 15 min or until 500 μL of milk was collected [ 33 ]. Milk samples were kept at −80 °C for further analysis.…”

The Comparison of Nutritional Value of Human Milk with Other Mammals’ Milk

“…Moreover, the newest data suggest that milk cholesterol concentration in mice is not affected by a high-cholesterol diet and conditions of maternal hypercholesterolaemia and is maintained at stable levels via ATP-binding cassette transporter G8 (ABCG8-) and LDL receptor (LDLR-) independent mechanisms [83]. The study in humans also showed that maternal diet does not change the ChC in breast milk [84].…”