Document Detail

Maternal cholestasis during pregnancy programs metabolic disease in offspring.
MedLine Citation:
PMID:  23934127     Owner:  NLM     Status:  MEDLINE    
The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.
Georgia Papacleovoulou; Shadi Abu-Hayyeh; Evanthia Nikolopoulou; Oscar Briz; Bryn M Owen; Vanya Nikolova; Caroline Ovadia; Xiao Huang; Marja Vaarasmaki; Marc Baumann; Eugene Jansen; Christiane Albrecht; Marjo-Riitta Jarvelin; Jose J G Marin; A S Knisely; Catherine Williamson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-06-24
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  123     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-08-12     Completed Date:  2013-10-01     Revised Date:  2013-10-06    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3172-81     Citation Subset:  AIM; IM    
Institute of Reproductive and Developmental Biology, Hammersmith Hospital, Imperial College London, London, United Kingdom.
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MeSH Terms
Adipose Tissue, White / metabolism
Bile Acids and Salts / metabolism
Blood Glucose
Case-Control Studies
Cells, Cultured
Cholestasis, Intrahepatic / complications*,  metabolism
Disease Susceptibility / etiology,  metabolism
Epigenesis, Genetic
Fatty Liver / etiology*,  metabolism
Insulin / blood
Lipid Metabolism
Liver / metabolism
Mice, Inbred C57BL
Obesity / etiology*,  metabolism
Placenta / metabolism
Pregnancy Complications / metabolism
Prenatal Exposure Delayed Effects / etiology*,  metabolism
Prenatal Nutritional Physiological Phenomena
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Bile Acids and Salts; 0/Blood Glucose; 0/Insulin
Comment In:
J Clin Invest. 2013 Jul 1;123(7):2786-8   [PMID:  23926602 ]

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