Maternal Hypercholesterolemia Research Articles

Maternal hypercholesterolaemia during pregnancy affects severity of myocardial infarction in young adults.

Elevated maternal cholesterol during pregnancy (MCP) enhances atherogenesis in childhood, but its possible impact on acute myocardial infarction (AMI) in adults is unknown. We retrospectively evaluated 310 patients who were admitted to hospital and whose MCP data were retrievable. Eighty-nine AMI patients with typical chest pain, transmural infarction Q-waves, elevated creatinine kinase, and 221 controls hospitalized for other reasons were identified. The AMI cohort was classified by MI severity (severe = involving three arteries, left ventricle ejection fraction ≤35, CK-peak >1200 mg/dL, or CK-MB >200 mg/dL). The association of MCP with AMI severity was tested by linear and multiple regression analysis that included conventional cardiovascular risk factors, gender, age, and treatment. Associations of MCP with body mass index (BMI) in patients were assessed by linear correlation. In the AMI cohort, MCP correlated with four measures of AMI severity: number of vessels (β = 0.382, P = 0.001), ejection fraction (β = -0.315, P = 0.003), CK (β = 0.260, P = 0.014), and CK-MB (β = 0.334, P = 0.001), as well as survival time (β = -0.252, P = 0.031). In multivariate analysis of patients stratified by AMI severity, MCP predicted AMI severity independently of age, gender, BMI, and CHD risk factors (odds ratio = 1.382, 95% confidence interval 1.046-1.825; P = 0.023). Survival was affected mainly by AMI severity. Maternal cholesterol during pregnancy is associated with adult BMI, atherosclerosis-related risk, and severity of AMI.

Maternal hyperlipidemia and spontaneous preterm delivery: a multi-centre cohort study

Background Hyperlipidemia is a precursor of inflammation and oxidative stress and suggested to be associated with adverse pregnancy outcomes such as preterm delivery. This study evaluated the association between maternal hyperlipidemia and spontaneous preterm delivery. Methods This was a prospective, multicentre cohort study in which 239 pregnant women aged 20–35 years with singleton pregnancy, were consecutively recruited at estimated gestational ages of 14–18weeks. Maternal serum lipids were determined at recruitment over a 2-month period and they were followed up until 37 weeks for the subsequent 6 months. Pregnant women with medical conditions and medications that could alter serum lipid levels were excluded from the study. Demographic and baseline variables were summarized using descriptive statistics. Comparison of continuous variables was done using the student’s t-test and categorical variables were compared using the Chi square or Fisher’s exact test as appropriate. Correlation was determined using Pearson’s correlation. Odd ratios were calculated at 95% confidence interval, width of CI as 10% (0.1) and all significances are reported at p < .05. Findings The prevalence of spontaneous preterm delivery and maternal hypercholesterolemia was 10.2% and 33.1% respectively. There was no significant association between spontaneous preterm delivery and hyperlipidemia in pregnancy (p = .102). Mean serum total cholesterol (mmol/L), LDL cholesterol (mmol/L), HDL cholesterol (mmol/L) and triglyceride (mmol/L) was 5.31 ± 0.84, 2.60 ± 0.72, 1.64 ± 0.36 and 1.23 ± 0.40 respectively in women with spontaneous preterm delivery was similar to mean values of 5.23 ± 0.98, 2.54 ± 0.82, 1.64 ± 0.49 and 1.30 ± 0.59 respectively in women with term delivery. There was no significant correlation between mean individual serum lipids, determined at 14–18weeks gestational age, and gestational age at delivery. Conclusion Serum lipid values determined early in pregnancy were observed to be similar in women with preterm and term delivery. There was no association between hyperlipidemia and spontaneous preterm delivery. There was no correlation of individual mean lipid values, determined early in pregnancy, and gestational age at delivery.

Management of familial hypercholesterolemia in pregnancy.

To highlight quandaries and review options for the management of familial hypercholesterolemia (FH) during pregnancy. Women with FH face barriers to effective care and consequently face significant disease related long term morbidity and mortality.Pregnancy includes major maternal physiological changes resulting in exacerbation of maternal hypercholesterolemia compounded by the current practice of cessation or reduction in the dose of lipid-lowering therapy during pregnancy and lactation that may impact short and long term cardiac morbidity and mortality. Although lipoprotein apheresis is the treatment of choice for high- risk FH patients, reassuring safety evidence for the use of statins during pregnancy is mounting rapidly. However, it will be some time before subtle effects on the development of the offspring can be definitively excluded. Women with homozygous FH or with an established atherosclerotic vessel or aortic disease should be offered therapy with statins during pregnancy if lipoprotein apheresis is not readily available. Pregnancy outcomes tend to be favourable in women with FH. We have reviewed the currently available evidence regarding the risks and benefits of treatment options for FH during pregnancy.

Maternal supraphysiological hypercholesterolemia is associated with increased levels of lipid peroxidation and an increased antioxidant capacity of maternal HDL, but not with changes in PON1 activity

Maternal supraphysiological hypercholesterolemia is associated with increased levels of lipid peroxidation and an increased antioxidant capacity of maternal HDL, but not with changes in PON1 activity

Supplementary materials for Cholesterol metabolism genetics, risk of maternal supraphysiological hypercholesterolemia: an analysis of maternal-fetal interaction

Supplementary materials for Cholesterol metabolism genetics, risk of maternal supraphysiological hypercholesterolemia: an analysis of maternal-fetal interaction

Increased Fetal Cardiovascular Disease Risk: Potential Synergy Between Gestational Diabetes Mellitus and Maternal Hypercholesterolemia.

Cardiovascular diseases (CVD) remain a major cause of death worldwide. Evidence suggests that the risk for CVD can increase at the fetal stages due to maternal metabolic diseases, such as gestational diabetes mellitus (GDM) and maternal supraphysiological hypercholesterolemia (MSPH). GDM is a hyperglycemic, inflammatory, and insulin-resistant state that increases plasma levels of free fatty acids and triglycerides, impairs endothelial vascular tone regulation, and due to the increased nutrient transport, exposes the fetus to the altered metabolic conditions of the mother. MSPH involves increased levels of cholesterol (mainly as low-density lipoprotein cholesterol) which also causes endothelial dysfunction and alters nutrient transport to the fetus. Despite that an association has already been established between MSPH and increased CVD risk, however, little is known about the cellular processes underlying this relationship. Our knowledge is further obscured when the simultaneous presentation of MSPH and GDM takes place. In this context, GDM and MSPH may substantially increase fetal CVD risk due to synergistic impairment of placental nutrient transport and endothelial dysfunction. More studies on the separate and/or cumulative role of both processes are warranted to suggest specific treatment options.

Maternally inherited hypercholesterolemia does not modify the cardiovascular phenotype in familial hypercholesterolemia

Background and aimsFamilial hypercholesterolemia (FH) is a codominant autosomal disease characterized by a high risk of cardiovascular disease when not in lipid-lowering treatment. However, there is a large variability in the clinical presentation in heterozygous subjects (HeFH). Maternal hypercholesterolemia has been proposed as a cardiometabolic risk factor later in life. Whether this phenotype variability depends on the mother or father origin of hypercholesterolemia is unknown.The objective of this study was to analyze potential differences in anthropometry, superficial lipid deposits, comorbidities, and lipid concentrations depending on the parental origin of hypercholesterolemia within a large group of HeFH. MethodsThis is a cross-sectional observational, multicenter, nation-wide study in Spain. We recruited adults with HeFH to study clinical differences according to the parental origin. Data on HeFH patients were obtained from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. ResultsHeFH patients were grouped in 1231 HeFH-mother-offspring aged 45.7 (16.3) years and 1174 HeFH-father-offspring aged 44.8 (16.7) years. We did not find any difference in lipid parameters (total cholesterol, triglycerides, LDLc, HDLc, and Lp(a)), nor in the comorbidities studied (cardiovascular disease prevalence, age of onset of cardiovascular disease, obesity, diabetes, and hypertension) between groups. Lipid-lowering treatment did not differ between groups. The prevalence of comorbidities did not show differences when they were studied by age groups. ConclusionsOur research with a large group of subjects with HeFH shows that a potential maternal effect is not relevant in FH. However, due to the size of our sample, potential differences between genders cannot be completely ruled out. This implies that severe maternal hypercholesterolemia during pregnancy is not associated with additional risk in the FH affected offspring.

Pomegranate juice supports therapeutic –treatment of atorvastatin against maternal hypercholesterolemia induced retinopathy of rat offspring

ABSTRACT Dietary consumption of processed high fat diet led to the development of metabolic diseases. This study aimed to demonstrate the retinopathy in a rat offspring maternally fed on high cholesterol and the improvement of pomegranate juice (PJ) administration and atorvastatin as potential treatment. Eighty pregnant Wistar albino rats were categorized into eight groups (n = 10); the control, PJ supplementation [0.4 m L (20%)]; atorvastatin-treatment (10 mg/kg); and hypercholesterolemia (fed on 3% cholesterol for 6 weeks prior to conception, during pregnancy and lactation period. Retinas of 21-day-old rat offspring were investigated. Offspring maternally fed on a hypercholesterolemic diet exhibited internal retinal hemorrhage at the interphase between the pigment epithelium and photoreceptors leading to retinal detachment. In addition, widespread of degenerated stacked membrane of the photoreceptor outer segment and the neovascularization within the nuclear layers were observed. Offspring retina of a hypercholesterolemic mother exhibited a significant depletion of assayed neurotransmitters coinciding with a significant increase of the vacuolar endothelial growth factor apoptotic markers expressing pressing damaging of retinal cells. Co-administration of pomegranate juice to hypercholesterolemic mother rats treated with atorvastatin significantly improved the retinal structure and the assayed biochemical markers of offspring than that with atorvastatin-treatment. In conclusion, PJ showed a potent antiapoptotic and ant- angiogenesis activity and improved the histocytological pictures of rat offspring maternally subjected to hypercholesterolemia.

Dyslipemias and pregnancy, an update

During pregnancy there is a physiological increase in total cholesterol (TC) and triglycerides (TG) plasma concentrations, due to increased insulin resistance, oestrogens, progesterone, and placental lactogen, although their reference values are not exactly known, TG levels can increase up to 300 mg/dL, and TC can go as high as 350 mg/dL. When the cholesterol concentration exceeds the 95th percentile (familial hypercholesterolaemia (FH) and transient maternal hypercholesterolaemia), there is a predisposition to oxidative stress in foetal vessels, exposing the newborn to a greater fatty streaks formation and a higher risk of atherosclerosis. However, the current treatment of pregnant women with hyperlipidaemia consists of a diet and suspension of lipid-lowering drugs.The most prevalent maternal hypertriglyceridaemia (HTG) is due to secondary causes, like diabetes, obesity, drugs, etc. The case of severe HTG due to genetic causes is less prevalent, and can be a higher risk of maternal-foetal complications, such as, acute pancreatitis (AP), preeclampsia, pre-eclampsia, preterm labour, and gestational diabetes. Severe HTG-AP is a rare but potentially lethal pregnancy complication, for the mother and the foetus, usually occurs during the third trimester or in the immediate postpartum period, and there are no specific protocols for its diagnosis and treatment.In conclusion, it is crucial that dyslipidaemia during pregnancy must be carefully evaluated, not just because of the acute complications, but also because of the future cardiovascular morbidity and mortality of the newborn child. That is why the establishment of consensus protocols or guidelines is essential for its management.

Maternal hypercholesterolemia exacerbates atherosclerosis lesions in female offspring through potentiating macrophage polarization toward an inflammatory M1 phenotype

Maternal hypercholesterolemia induces early onset of cardiovascular diseases in offspring; however, its underlying mechanism remains poorly understood. We hypothesized that maternal hypercholesterolemia increases offspring susceptibility to atherosclerosis in adulthood through developmental modifications of macrophages. Female apolipoprotein E (ApoE)-deficient mice were fed a Western-type diet (WD) or a control diet (CD) prior to and throughout gestation and lactation. The offspring were all fed a WD after weaning. Sixteen-week-old female offspring of WD-fed dams showed a significant increase in atherosclerotic lesions of the aorta and aortic root compared with those of CD-fed dams. This effect was associated with increased macrophage accumulation within lesions, macrophage inflammation and an increase in circulating Ly6Chigh monocyte and F4/80 macrophage counts. We further evidenced that in utero WD exposure promoted macrophage polarization toward the M1 phenotype by elevating M1 markers (Cd86, Inos/Nos2) without affecting M2 markers (Cd206, Arg1). Proinflammatory cytokine synthesis was also enhanced in response to LPS. Finally, maternal WD intake strongly inhibited the macrophage expression of Pparg and Lxra, which was associated with aberrant DNA methylation of Lxra promoter. Our findings demonstrate that maternal hypercholesterolemia exacerbates atherosclerosis, in part by altering the epigenetic state of the macrophage genome of the offspring, imprinting gene expression, and changing macrophage polarization, which ultimately contributes to plaque macrophage burden.

Dislipemias y embarazo, una puesta al día

During pregnancy there is a physiological increase in total cholesterol (TC) and triglycerides (TG) plasma concentrations, due to increased insulin resistance, oestrogens, progesterone, and placental lactogen, although their reference values are not exactly known, TG levels can increase up to 300mg/dL, and TC can go as high as 350mg/dL. When the cholesterol concentration exceeds the 95th percentile (familial hypercholesterolaemia (FH) and transient maternal hypercholesterolaemia), there is a predisposition to oxidative stress in foetal vessels, exposing the newborn to a greater fatty streaks formation and a higher risk of atherosclerosis. However, the current treatment of pregnant women with hyperlipidaemia consists of a diet and suspension of lipid-lowering drugs.The most prevalent maternal hypertriglyceridaemia (HTG) is due to secondary causes, like diabetes, obesity, drugs, etc. The case of severe HTG due to genetic causes is less prevalent, and can be a higher risk of maternal-foetal complications, such as, acute pancreatitis (AP), pre-eclampsia, preterm labour, and gestational diabetes. Severe HTG-AP is a rare but potentially lethal pregnancy complication, for the mother and the foetus, usually occurs during the third trimester or in the immediate postpartum period, and there are no specific protocols for its diagnosis and treatment.In conclusion, it is crucial that dyslipidaemia during pregnancy must be carefully evaluated, not just because of the acute complications, but also because of the future cardiovascular morbidity and mortality of the newborn child. That is why the establishment of consensus protocols or guidelines is essential for its management.

Maternal cholesterol levels during gestation: boon or bane for the offspring?

An increase in cholesterol levels is perceived during pregnancy and is considered as a normal adaptive response to the development of the fetus. In some pregnancies, excessive increase in total cholesterol with high levels of Low-Density Lipoprotein leads to maladaptation by the fetus to cholesterol demands, resulting in a pathological condition termed as maternal hypercholesterolemia (MH). MH is considered clinically irrelevant and therefore cholesterol levels are not routinely checked during pregnancy, as a consequence of which there is scarce information on its global prevalence in pregnant women. Studies have reported that MH during pregnancy can cause atherogenesis in adults emphasizing the concept of in utero programming of fetus. Moreover, Gestational Diabetes Mellitus, obesity and Polycystic Ovary Syndrome are potential risk factors which strengthen combined pathologies in placenta and fetuses of mothers with MH. However, lack of conclusive evidence on cholesterol transport and underlying programming demand substantial research to develop population-based life style strategies for women in their childbearing years. The current review focuses on the mechanisms and outcomes of MH from existing epidemiological as well as experimental data and presents a detailed insight on this novel risk factor of cardiovascular diseases.

Maternal hypercholesterolemia programs dyslipidemia in adult male mouse progeny.

As a collection of metabolic abnormalities including inflammation, insulin resistance, hypertension, hormone imbalance, and dyslipidemia, maternal obesity has been well-documented to program disease risk in adult offspring. Although hypercholesterolemia is strongly associated with obesity, less work has examined the programming influence of maternal hypercholesterolemia (MHC) independent of maternal obesity or high-fat feeding. This study was conducted to characterize how MHC per se impacts lipid metabolism in offspring. Female (n = 6/group) C57BL/6J mice were randomly assigned to: (1.) a standard chow diet (Control, CON) or (2.) the CON diet supplemented with exogenous cholesterol (CH) (0.15%, w/w) throughout mating and the gestation and lactation periods. At weaning (postnatal day (PND) 21) and adulthood (PND 84), male offspring were characterized for blood lipid and lipoprotein profile and hepatic lipid endpoints, namely cholesterol and triglyceride (TG) accumulation, fatty acid profile, TG production, and mRNA expression of lipid-regulatory genes. Both newly weaned and adult offspring from CH mothers demonstrated increased very low-density lipoprotein (VLDL) particle number and size and hepatic TG and n-6 polyunsaturated fatty acid accumulation. Further, adult CH offspring exhibited reduced fatty acid synthase (Fasn) and increased diglyceride acyltransferase (Dgat1) mRNA expression. These programming effects appear to be independent of changes in hepatic TG production and postprandial lipid clearance. Study results suggest that MHC, independent of obesity or high-fat feeding, can induce early changes to serum VLDL distribution and hepatic lipid profile that persist into adulthood.

A Review of the Association of Cardiovascular Diseases and Maternal &amp; Offspring Health Risk Factors

Abstract Objectives Since cardiovascular disease (CVD) is considered to be one of the most expanding collections of health disorders in terms of severity and progression, the relationship of maternal and offspring health risk factors with CVD needs study. The objective of this review was to identify how developmental origin and maternal health are related to disease progression in both mothers and their offspring, apart from general risk factors such as lifestyle, eating behavior and genetic factors. Methods A computer based literature search through PubMed, Medline, Google Scholar and Google Search was carried out. The keywords for searching included maternal health, cardiovascular diseases, maternal and offspring cardiovascular health and developmental origin. Results Increasing evidence demonstrates that women with pregnancy-related complications, such as preeclampsia, preterm birth and maternal hypertension, are at risk for CVD in any phase of their life. Further, maternal malnutrition plays an influential role in the progression of CVD in the adulthood of their offspring. Also, in-utero exposure to high cholesterol or maternal hypercholesterolemia can demonstrate early lesion of atherosclerosis in children. Conclusions A clearer perception on how different domains of maternal health complications independently or synergistically lead to CVD or vice-versa, as well as their impact on offspring's wellbeing, is required. This will assist in developing new preventive techniques and therapeutic treatments for CVD. Funding Sources Texas Tech University.

Excessive early-life cholesterol exposure may have later-life consequences for nonalcoholic fatty liver disease.

The in utero and immediate postnatal environments are recognized as critical windows of developmental plasticity where offspring are highly susceptible to changes in the maternal metabolic milieu. Maternal hypercholesterolemia (MHC) is a pathological condition characterized by an exaggerated rise in maternal serum cholesterol during pregnancy which can program metabolic dysfunction in offspring, including dysregulation of hepatic lipid metabolism. Although there is currently no established reference range MHC, a loosely defined cutoff point for total cholesterol >280 mg/dL in the third trimester has been suggested. There are several unanswered questions regarding this condition particularly with regard to how the timing of cholesterol exposure influences hepatic lipid dysfunction and the mechanisms through which these adaptations manifest in adulthood. Gestational hypercholesterolemia increased fetal hepatic lipid concentrations and altered lipid regulatory mRNA and protein content. These early changes in hepatic lipid metabolism are evident in the postweaning environment and persist into adulthood. Further, changes to hepatic epigenetic signatures including microRNA (miR) and DNA methylation are observed in utero, at weaning, and are evident in adult offspring. In conclusion, early exposure to cholesterol during critical developmental periods can predispose offspring to the early development of nonalcoholic fatty liver disease (NAFLD) which is characterized by altered regulatory function beginning in utero and persisting throughout the life cycle.

Maternal hypercholesterolemia during pregnancy: Potential modulation of cholesterol transport through the human placenta and lipoprotein profile in maternal and neonatal circulation

During pregnancy, there is a progressive increase in the levels of maternal cholesterol, a lipid that is essential for foetal growth and development. This increase can occur in a physiological (MPH) or supraphysiological (MSPH) manner, where MSPH is associated with detrimental effects on the mother and foetus, including endothelial dysfunction, oxidative stress, and atherosclerosis. Cholesterol is transported from the maternal to the foetal circulation through the placenta by a process that encompasses two main events: cholesterol uptake and efflux. The main receptors and transporters that participate in cholesterol transport are expressed in the human placenta, and their regulation in normal and pathological pregnancies has been evaluated. However, whether elevated levels of cholesterol induce these detrimental changes and whether their expression and function changes in the MSPH condition is still under study, along with the cell types involved in placental cholesterol traffic. Moreover, aside from cholesterol levels, the composition and function of lipoproteins have recently become important to study as these factors may also contribute to the atherogenic process. There is information regarding the maternal and neonatal lipoproteins profile and their changes during pregnancy. However, there are no reports that evaluate the changes of these lipoproteins in MSPH pregnancies. The latter could be relevant considering the consequences that MSPH has on the foetal vasculature. In this review, we summarize the available information regarding cholesterol transport through the placenta and the metabolism of maternal and neonatal lipoproteins in MPH and MSPH conditions, suggesting the importance of increasing our knowledge about these conditions and the monitoring of maternal cholesterol levels during pregnancy.

Cholesterol uptake and efflux are impaired in human trophoblast cells from pregnancies with maternal supraphysiological hypercholesterolemia

Maternal physiological (MPH) or supraphysiological hypercholesterolaemia (MSPH) occurs during pregnancy. Cholesterol trafficking from maternal to foetal circulation requires the uptake of maternal LDL and HDL by syncytiotrophoblast and cholesterol efflux from this multinucleated tissue to ApoA-I and HDL. We aimed to determine the effects of MSPH on placental cholesterol trafficking. Placental tissue and primary human trophoblast (PHT) were isolated from pregnant women with total cholesterol <280 md/dL (MPH, n = 27) or ≥280 md/dL (MSPH, n = 28). The lipid profile in umbilical cord blood from MPH and MSPH neonates was similar. The abundance of LDL receptor (LDLR) and HDL receptor (SR-BI) was comparable between MSPH and MPH placentas. However, LDLR was localized mainly in the syncytiotrophoblast surface and was associated with reduced placental levels of its ligand ApoB. In PHT from MSPH, the uptake of LDL and HDL was lower compared to MPH, without changes in LDLR and reduced levels of SR-BI. Regarding cholesterol efflux, in MSPH placentas, the abundance of cholesterol transporter ABCA1 was increased, while ABCG1 and SR-BI were reduced. In PHT from MSPH, the cholesterol efflux to ApoA-I was increased and to HDL was reduced, along with reduced levels of ABCG1, compared to MPH. Inhibition of SR-BI did not change cholesterol efflux in PHT. The TC content in PHT was comparable in MPH and MSPH cells. However, free cholesterol was increased in MSPH cells. We conclude that MSPH alters the trafficking and content of cholesterol in placental trophoblasts, which could be associated with changes in the placenta-mediated maternal-to-foetal cholesterol trafficking.

Natural cocoa improves birth weight and viability of rabbit pups born to hypercholesterolemic mothers

BackgroundMaternal nutrition affects fetal growth and development in humans and animals. Low birth weight can be caused by maternal hypercholesterolemia and is associated with increased risk of cardiovascular and other metabolic diseases later in adult life. Cocoa powder is rich in flavonoids and reduces plasma cholesterol levels. The study investigated the effect of hypercholesterolemia and natural cocoa intake during pregnancy on the birth weight and viability of rabbit pups. MethodsHypercholesterolemic female New Zealand White rabbits were crossed with normocholesterolemic males and randomly grouped into 2 (n = 4 each). One group (HCC) received natural cocoa powder in their water in addition to high cholesterol diet during pregnancy, whereas the other (HC) received only water and high cholesterol diet. Litter size, birth weight and viability of pups were assessed and compared to a control group (NC) fed normal rabbit chow (n = 2). ResultsAverage litter sizes of hypercholesterolemic rabbits (HC and HCC groups) were 3, whereas that of control group, NC was 5. Mean birth weight of pups was significantly lower in offspring of HC (42.73 g, SD 8.47) and HCC (50.0 g, SD 3.54) as compared to NC (73.0 g, SD 5.37). Mortality of offspring was highest in HC group (58.3%) as compared to 50% in HCC. ConclusionsMaternal hypercholesterolemia during pregnancy reduces litter size, birth weight and viability of offspring in rabbits and these deleterious effects may be minimized by regular intake of natural cocoa. Although further studies in humans need to be conducted, the results of this study suggest the need to monitor maternal cholesterol levels during pregnancy and the effects on pregnancy outcomes and health of offspring later in life.

The nonalcoholic fatty liver disease-like phenotype and lowered serum VLDL are associated with decreased expression and DNA hypermethylation of hepatic ApoB in male offspring of ApoE deficient mothers fed a with Western diet

Increasing evidence indicates that the intra-uterine environment has consequences for later life. However, the mechanisms of this fetal programming remain unclear. We aimed to investigate the impact of diet-induced maternal hypercholesterolemia on the predisposition of offspring to nonalcoholic fatty liver diseases (NAFLD) and metabolic diseases and its underlying mechanisms. Female apolipoprotein (Apo) E-deficient mice were fed a control diet (CD) or high fat/high cholesterol Western-type diet (WD) before and throughout pregnancy and lactation, and their offspring were weaned onto a CD postnatally. Strikingly, male offspring of WD-fed dams developed glucose intolerance and decreased peripheral insulin sensitivity and exhibited hepatic steatosis. Hepatic steatosis could be attributed, at least in part, to increased hepatic lipogenesis in E18.5 embryos and decreased serum VLDL levels in adulthood. In addition, males born to WD-fed dams had lower serum ApoB levels and hepatic ApoB gene expression compared with males born to CD-fed dams. DNA methylation analysis revealed increased methylation of CpG dinucleotides on the promoter region of the ApoB genes in the livers of male offspring of WD-fed dams. Our findings suggest that maternal WD intake can exacerbate the development of NAFLD in male offspring potentially by affecting ApoB gene expression through epigenetic alterations.

Lipidomic profiles of maternal blood at the earlier stage of gestation and umbilical venous blood in response to supraphysiological hypercholesterolemia versus physiological hypercholesterolemia: An evidence of potential biomarkers and early intervention

BackgroundTo our knowledge, we lack a complete understanding of the lipidomes alterations caused by maternal supraphysiological hypercholesterolemia (MSPH) at the third trimester. ObjectivesThe aim of this study was to investigate lipidomes alterations in maternal and umbilical venous (UV) serum and explore the association between these alterations and MSPH. MethodsWe conducted a nest case-control study between maternal physiological hypercholesterolemia (MPH) and MSPH subjects during pregnancy. Lipidomic profiling of maternal serum at the first trimester of gestation and UV serum was performed by ultra-high-performance liquid chromatography system connected to a quadrupole time-of-light/mass spectrometer. ResultsSeveral glycerophospholipids and sphingolipids (C18 sphingoid base) species were distinctly altered in maternal serum and/or UV serum with MSPH versus MPH. Glycerophospholipid metabolism, sphingolipid metabolism and propanoate metabolism were the main pathways that involved the most of discriminate metabolites. Higher HDL-c and phosphatidylcholine (16:0/0:0) (PC (16:0/0:0)) during pregnancy, higher PC (16:0/0:0) and lower cholesterol ester 20:4(8Z,11Z,14Z,17Z) (CE (20:4(8Z,11Z,14Z,17Z))) in the UV serum may be the risk factors for the increased placental circulation resistance. The total cholesterol levels of maternal serum both at the first trimester and at the third trimester were significantly correlated with some lipid species of UV serum. ConclusionThis study clarifies the differential lipid profiles to distinguish MSPH from MPH and the pathway which is influenced under the condition of MSPH. Also, it provides a resource to look for potential therapeutic targets for MSPH.