Maternal cholestasis during pregnancy programs metabolic disease in offspring

Papacleovoulou, Georgia; Abu-Hayyeh, Shadi; Nikolopoulou, Evanthia; Briz, Oscar; Owen, Bryn M.; Nikolova, Vanya; Ovadia, Caroline; Huang, Xiao; Vaarasmaki, Marja; Baumann, Marc; Jansen, Eugene; Albrecht, Christiane; Jarvelin, Marjo-Riitta; Marin, Jose J. G.; Knisely, A. S.; Williamson, Catherine (2013). Maternal cholestasis during pregnancy programs metabolic disease in offspring. Journal of clinical investigation, 123(7), pp. 3172-3181. American Society for Clinical Investigation 10.1172/JCI68927

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine

UniBE Contributor:

Baumann, Marc and Albrecht, Christiane

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

0021-9738

Publisher:

American Society for Clinical Investigation

Language:

English

Submitter:

Patrizia Catucci

Date Deposited:

30 Apr 2014 11:53

Last Modified:

13 Dec 2014 13:33

Publisher DOI:

10.1172/JCI68927

PubMed ID:

23934127

BORIS DOI:

10.7892/boris.43271

URI:

https://boris.unibe.ch/id/eprint/43271

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