Document Detail


Maternal obesity during pregnancy and lactation programs the development of offspring non-alcoholic fatty liver disease in mice.
MedLine Citation:
PMID:  20413174     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Obesity induced, non-alcoholic fatty liver disease (NAFLD), is now the major cause in affluent countries, of the spectrum of steatosis-to-cirrhosis. Obesity and NAFLD rates in reproductive age women, and adolescents, are rising worldwide. Our hypothesis was that maternal obesity and lactation transmit to the offspring a pre-disposition to dysmetabolism, obesity and NAFLD. METHODS: Female mice were fed standard or obesogenic chow, before, throughout pregnancy, and during lactation. The critical developmental period was studied by cross-fostering offspring of lean and obese dams. Offspring were then weaned onto standard chow and studied at 3months. Read-outs included markers of metabolic dysfunction, biochemical and histological indicators of NAFLD, induction of liver fibrogenesis, and activation of pro-fibrotic pathways. Mechanisms involved in programming a dysmetabolic and NAFLD phenotype were investigated by assaying breast milk components. RESULTS: Offspring of obese dams had a dysmetabolic, insulin resistant and NAFLD phenotype compared to offspring of lean dams. Offspring of lean dams that were suckled by obese dams showed an exaggerated dysmetabolic and NAFLD phenotype, with increased body weight, as well as increased levels of insulin, leptin, aspartate transaminase, interleukin-6, tumour necrosis factor-alpha, liver triglycerides, steatosis, hepatic fibrogenesis, renal norepinephrine, and liver alpha1-D plus beta1-adrenoceptors, indicative of sympathetic nervous system activation. Obese dams also had raised breast milk leptin levels compared to lean dams. CONCLUSIONS: Maternal obesity programs development of a dysmetabolic and NAFLD phenotype, which is critically dependent on the early postnatal period and possibly involving alteration of hypothalamic appetite nuclei signalling by maternal breast milk and neonatal adipose tissue derived, leptin.
Authors:
Jude A Oben; Angelina Mouralidarane; Anne-Maj Samuelsson; Phillippa J Matthews; Maelle L Morgan; Chad McKee; Junpei Soeda; Denise S Fernandez-Twinn; Malgorzata S Martin-Gronert; Susan E Ozanne; Barbara Sigala; Marco Novelli; Lucilla Poston; Paul D Taylor
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Publication Detail:
Type:  Journal Article     Date:  2010-04-01
Journal Detail:
Title:  Journal of hepatology     Volume:  52     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-24     Completed Date:  2010-08-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  913-20     Citation Subset:  IM    
Copyright Information:
Copyright 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Affiliation:
University College London, Centre for Hepatology, Royal Free Hospital, London, UK. j.oben@ucl.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Actins / genetics
Adipose Tissue / metabolism
Animals
Collagen / genetics
Fatty Liver / etiology*,  pathology,  physiopathology
Female
Gene Expression / physiology
Interleukin-6 / genetics
Lactation*
Leptin / metabolism
Metabolic Syndrome X / etiology*,  pathology,  physiopathology
Mice
Mice, Inbred C57BL
Milk / metabolism
Obesity / complications*,  metabolism,  physiopathology
Pregnancy
Pregnancy Complications / metabolism,  pathology,  physiopathology*
Prenatal Exposure Delayed Effects / metabolism,  pathology,  physiopathology*
Receptors, Adrenergic, alpha-1 / genetics
Signal Transduction / physiology
Tumor Necrosis Factor-alpha / genetics
Chemical
Reg. No./Substance:
0/Actins; 0/Interleukin-6; 0/Leptin; 0/Receptors, Adrenergic, alpha-1; 0/Tumor Necrosis Factor-alpha; 0/adrenergic receptor alpha(1b); 0/adrenergic receptor alpha(1d); 0/alpha 2(I) collagen; 9007-34-5/Collagen
Comments/Corrections
Comment In:
J Hepatol. 2010 Jun;52(6):788-90   [PMID:  20392513 ]

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