Exposure to complement induced preeclampsia promotes fetal steatosis
暴露于补体诱发的先兆子痫会促进胎儿脂肪变性
基本信息
- 批准号:10740802
- 负责人:
- 金额:$ 16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-02 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:AccountingAdultAffectBeesBirth WeightBlood CirculationBody mass indexCardiovascular DiseasesChildChildhoodCholesterolCholesterol EstersChylomicronsCoagulation ProcessComplementControl GroupsDepositionDevelopmentDown-RegulationEnvironmentExperimental Animal ModelExposure toFatty LiverFatty acid glycerol estersFemaleFetal DevelopmentFetal Growth RetardationFetal LiverFetusFibrinFutureGene ExpressionGene Expression RegulationGenesGestational AgeGrowthHealthHepaticHepatocyteHigh Density LipoproteinsHumanHypertensionIL-6 inhibitorImpairmentLaboratoriesLinkLipidsLiverLiver CirrhosisLiver FibrosisLiver diseasesLow-Density LipoproteinsMalnutritionMediatingMetabolicMetabolic DiseasesMetabolic syndromeMusNeonatalNonesterified Fatty AcidsNutritionalObesityOutcome StudyOvernutritionPathway interactionsPhenotypePhysiologicalPlacentaPre-EclampsiaPregnancyPregnant WomenPremature MortalityPrevalencePrimary carcinoma of the liver cellsResearchRiskRisk FactorsRodentSex DifferencesSignal PathwaySignal TransductionSourceTNF geneTestingTimeTissue-Specific Gene ExpressionTriglyceridesUp-RegulationValidationVery low density lipoproteinWomancomorbiditycytokinedisorder riskfatty acid oxidationfetalgene repressioninflammatory milieuinhibitorinsightinsulin secretionintrauterine environmentlipid biosynthesislipid metabolismliver metabolismliver transplantationmalematernal obesitymouse modelnon-alcoholic fatty liver diseasenonalcoholic steatohepatitisnonhuman primatenovelnutritionoffspringoxidationpostnatalpregnantprenatalpreventreceptorsexuptake
项目摘要
Abstract:
Now it is well recognized that exposure to adverse intrauterine environment can greatly affect the
health postnatally and in adulthood. Exposure to maternal obesity during gestation is linked to
offspring adiposity, premature mortality from cardiovascular disease and hepatic steatosis in
humans. Evidence from different experimental animal models including rodents and non-human
primates strongly suggests that exposure to maternal overnutrition during gestation promotes fetal
hepatic fat storage (steatosis) with a long-lasting metabolic consequence for offspring.
In contrast to steatosis in adults where increased hepatic de novo lipogenesis and decreased fatty
acid oxidation are observed, steatosis in fetuses exposed to maternal obesity is predominantly
due to increased transplacental fuel transfer since increased de novo lipogenesis is not observed
in them. Increased hepatic de novo cholesterol synthesis and its decreased clearance were also
observed in adult NAFLD/NASH. Regardless of the source of lipids, obesity associated steatosis
in both prenatal and adults is characterized by overwhelming hepatic lipid load surpassing
hepatocyte lipid metabolic contingency.
In contrast to nutrition rich intrauterine environment of maternal obesity, PE is often associated
with reduced nutritional supply to the developing fetus and consequent intrauterine growth
restriction (IUGR). Prevalence of NAFLD is about 4 times higher in children after IUGR compared
to those with normal birth weight. Adulthood NAFLD is independent of childhood body mass index
and insulin secretion ruling out catch-up growth as the sole reason for NAFLD. The mechanism
linking IUGR to adulthood NAFLD is not known. Under normal physiological conditions two
important sources for liver lipids including cholesterol are de novo synthesis and receptor
mediated import from blood circulation. Since liver is not a lipid storage depot, liver lipids are
utilized in β-oxidation or secreted out mainly as very low-density lipoproteins (VLDL). Cholesterol
is an obligate component of VLDL and required for VLDL secretion from the liver. Based on these
observations we hypothesize that in IUGR fetuses steatosis occurs due to increased import of
lipids accompanied by the deficiency of cholesterol and impaired VLDL secretion. Fetal liver
steatosis could prime the liver for later liver metabolic diseases through similar mechanisms as
involved in maternal obesity associated adulthood NAFLD.
In this application we propose to understand fetal liver lipid metabolism under IUGR using a novel
PE mouse model we recently developed in our laboratory.
文摘:
项目成果
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Manu Banadakoppa其他文献
Manu Banadakoppa的其他文献
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{{ truncateString('Manu Banadakoppa', 18)}}的其他基金
Evaluating role of complement activation induced signaling pathways in preeclampsia pathology using a novel complement activation-based mouse model
使用基于补体激活的新型小鼠模型评估补体激活诱导的信号通路在先兆子痫病理学中的作用
- 批准号:
10521835 - 财政年份:2022
- 资助金额:
$ 16万 - 项目类别:
Evaluating role of complement activation induced signaling pathways in preeclampsia pathology using a novel complement activation-based mouse model
使用基于补体激活的新型小鼠模型评估补体激活诱导的信号通路在先兆子痫病理学中的作用
- 批准号:
10644021 - 财政年份:2022
- 资助金额:
$ 16万 - 项目类别:
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