Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal Absorption of Cholesterol in Adult Mice

Dimova, Lidiya G.; Boer, Jan Freark de; Plantinga, J.A.; Plösch, Torsten; Hoekstra, Menno; Verkade, Henkjan J.; Tietge, Uwe J. F.

doi:10.1053/j.gastro.2017.04.019

Cited by 13 publications

(16 citation statements)

References 18 publications

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“…Gene expression was analysed by quantitative real-time PCR as previously described (16) . Cyclophilin and 36b4 were used as housekeeping genes for hepatic and adipose tissue gene expression, respectively.…”

Section: Analysis Of Gene Expressionmentioning

confidence: 99%

Programming effects of an early life diet containing large phospholipid-coated lipid globules are transient under continuous exposure to a high-fat diet

et al. 2019

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Breast-feeding is associated with a lower risk of developing obesity during childhood and adulthood compared with feeding infant milk formula (IMF). Previous studies have shown that an experimental IMF (eIMF; comprising Nuturis®) programmed mouse pups for a lower body weight and fat mass gain in adulthood when challenged with a high-fat diet (HFD) compared with a control IMF (cIMF). Nuturis has a lipid composition and structure more similar to breast milk. Here, the long-term effects were tested of a similar eIMF, but with an adapted lipid composition and a cIMF, on body weight, glucose homoeostasis, liver and adipose tissue. Nutrient composition was similar for the eIMF and cIMF; the lipid fractions comprised approximately 50 % milk fat. C57BL/6JOlaHsd mice were fed cIMF or eIMF from postnatal day (PN) 16–42 followed by an HFD until PN168. Feeding eIMF v. cIMF in early life resulted in a lower body weight (–9 %) and body fat deposition (–14 %) in adulthood (PN105). The effect appeared transient, as from PN126 onwards, after 12 weeks’ HFD, eIMF-fed mice caught up on controls and body and fat weights became comparable between groups. Glucose and energy metabolism were similar between groups. At dissection (PN168), eIMF-fed mice showed larger (+27 %) epididymal fat depots and a lower (–26 %) liver weight without clear morphological aberrations. Our data suggest the size and coating but not the lipid composition of IMF fat globules underlie the programming effect observed. Prolonged exposure to an HFD challenge partly overrules the programming effect of early diet.

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Section: Analysis Of Gene Expressionmentioning

confidence: 99%

Programming effects of an early life diet containing large phospholipid-coated lipid globules are transient under continuous exposure to a high-fat diet

et al. 2019

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“…This has led to the hypothesis that early life cholesterol supply can program cholesterol homeostasis in later life. In support of this notion, we recently reported indications that dietary cholesterol availability in early life of mice determines the set-point for cholesterol absorption efficiency at adult age 7 . The rather strictly regulated concentration of milk cholesterol found in this study could support the relevance of a stable cholesterol supply for its programming importance.…”

Section: Discussionmentioning

confidence: 76%

“…The lower plasma cholesterol concentrations in adulthood may relate to long-term cardio-protective effects of breast milk, in accordance with the metabolic programming hypothesis 1 , 6 . Additionally, we recently demonstrated that maternal ezetimibe-induced lower dietary cholesterol bioavailability during the lactation period in mice decreases cholesterol absorption in the offspring up to adulthood through decreased intestinal NPC1L1 expression 7 .…”

Section: Introductionmentioning

confidence: 99%

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

Dimova

Lohuis

Bloks

et al. 2018

Sci Rep

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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.

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“…cDNA was synthesized using M-MLV (Invitrogen, Breda, the Netherlands) and random nonamers (Sigma). cDNA was quantified by relative standard curves using quantitative real-time PCR as previously described [16]. Primer and TaqMan probe sequences are given in S2 Table.…”

Section: Methodsmentioning

confidence: 99%

Spontaneous liver disease in wild-type C57BL/6JOlaHsd mice fed semisynthetic diet

Ronda

Heijning

Bruin

et al. 2020

Preprint

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Mouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism. In male C57BL/6JOlaHsd mice fed AIN-93G from birth to postnatal day (PN)70, we measured plasma BA, lipids, Very low-density lipoprotein (VLDL)-triglyceride (TG) secretion, and hepatic mRNA expression patterns. Mice were sacrificed at PN21, PN42, PN63 and PN70. Liver weight distribution was bimodal at PN70. Mice could be subdivided into two nonoverlapping groups based on liver weight: 0.6 SD 0.1 g (approximately one-third of mice, small liver; SL), and 1.0 SD 0.1 g (normal liver; NL; p<0.05). Liver histology showed a higher steatosis grade, inflammation score, more mitotic figures and more fibrosis in the SL versus the NL group. Plasma BA concentration was 14-fold higher in SL (p<0.001). VLDL-TG secretion rate was lower in SL mice, both absolutely (−66%, p<0.001) and upon correction for liver weight (−44%, p<0.001). Mice that would later have the SL-phenotype showed lower food efficiency ratios during PN21-28, suggesting the cause of the SL phenotype is present at weaning (PN21). Our data show that approximately one-third of C57BL/6JOlaHsd mice fed semisynthetic diet develop spontaneous liver disease with aberrant histology and parameters of hepatic lipid, bile acid and lipoprotein metabolism. Study designs involving this mouse strain on semisynthetic diets need to take the SL phenotype into account. Plasma lipids may serve as markers for the identification of the SL phenotype.

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Inhibiting Cholesterol Absorption During Lactation Programs Future Intestinal Absorption of Cholesterol in Adult Mice

Cited by 13 publications

References 18 publications

Programming effects of an early life diet containing large phospholipid-coated lipid globules are transient under continuous exposure to a high-fat diet

Programming effects of an early life diet containing large phospholipid-coated lipid globules are transient under continuous exposure to a high-fat diet

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

Spontaneous liver disease in wild-type C57BL/6JOlaHsd mice fed semisynthetic diet

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