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Bisphenol A exposure increases liver fat in juvenile fructose-fed Fischer 344 rats
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
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2013 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 303, no 1, 125-132 p.Article in journal (Refereed) Published
Abstract [en]


Prenatal exposure to bisphenol A (BPA) has been shown to induce obesity in rodents. To evaluate if exposure also later in life could induce obesity or liver damage we investigated these hypothesises in an experimental rat model.


From five to fifteen weeks of age, female Fischer 344 rats were exposed to BPA via drinking water (0.025, 0.25 or 2.5mgBPA/L) containing 5% fructose. Two control groups were given either water or 5% fructose solution. Individual weight of the rats was determined once a week. At termination magnetic resonance imaging was used to assess adipose tissue amount and distribution, and liver fat content. After sacrifice the left perirenal fat pad and the liver were dissected and weighed. Apolipoprotein A-I in plasma was analyzed by western blot.


No significant effects on body weight or the weight of the dissected fad pad were seen in rats exposed to BPA, and MRI showed no differences in total or visceral adipose tissue volumes between the groups. However, MRI showed that liver fat content was significantly higher in BPA-exposed rats than in fructose controls (p=0.04). BPA exposure also increased the apolipoprotein A-I levels in plasma (p<0.0001).


We found no evidence that BPA exposure affects fat mass in juvenile fructose-fed rats. However, the finding that BPA in combination with fructose induced fat infiltration in the liver at dosages close to the current tolerable daily intake (TDI) might be of concern given the widespread use of this compound in our environment.

Place, publisher, year, edition, pages
2013. Vol. 303, no 1, 125-132 p.
Keyword [en]
MRI, Liver fat, Rat, Bisphenol A, Obesity
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-185549DOI: 10.1016/j.tox.2012.09.013ISI: 000314856800014PubMedID: 23142792OAI: oai:DiVA.org:uu-185549DiVA: diva2:572054
Available from: 2012-11-08 Created: 2012-11-26 Last updated: 2015-03-25Bibliographically approved
In thesis
1. Environmental Contaminants and Obesity
Open this publication in new window or tab >>Environmental Contaminants and Obesity
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obesity is a worldwide problem affecting both children and adults. Genetic, physiological, environmental, psychological, social and economic factors interact in varying degrees, influencing body weight and fat distribution and the progress of obesity. Moreover, some anthropogenic chemicals have proven to be endocrine disrupting chemicals (EDCs) with the potential to interfere with different actions of hormones in the body. EDCs may thereby disrupt homeostasis, modifying developmental, behavioral and immune functions in humans and animals, and also promoting adiposity. Because hormones generally act at low concentrations, small changes in the endocrine system may lead to extensive effects. Based on data from experimental and epidemiological studies this thesis elucidates the relationship between a large number of environmental contaminants and obesity.

The experimental studies demonstrated that fructose supplementation in the drinking water resulted in unfavorable metabolic alterations such as a higher liver somatic index (LSI), an increase in plasma triglycerides and increased plasma levels of apo A-I. Fructose in combination with exposure to bisphenol A (BPA) increased liver fat content and plasma levels of apo A-I in juvenile female Fischer 344 rats. The experimental studies also showed that the retro-peritoneal fat, which in rats is a distinct fat depot easy to distinguish and dissect, correlated well with the measurements of total fat mass analyzed with MRI, and could therefore be used as a substitute for total fat mass in rats.

The epidemiological studies showed that circulating levels of persistent organic pollutants (POPs) were related to fat mass measured by DXA. OCDD, HCB, TNC, DDE and the less chlorinated PCBs were positively related to fat mass, while the more highly chlorinated PCBs showed a negative association. Further, circulating levels of BPA were positively associated with levels of the hormones adiponectin and leptin, but negatively related with ghrelin, hormones which are involved in the regulation of hunger and satiety. However, serum BPA levels were not related to measures of fat mass in the elderly individuals in the PIVUS cohort.

This thesis concludes that environmental contaminants such as BPA and POPs most likely are contributors, along with genetic, social and behavioral factors, to the development of obesity.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 67 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 949
Fischer 344, rat, obesity, adipose tissue, persistent organic pollutants, POPs, bisphenol A, BPA, pesticides, dioxin, PCB, DDT, apo A-I, adiponectin, leptin, ghrelin
National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-209807 (URN)978-91-554-8798-0 (ISBN)
Public defence
2013-12-13, Frödingsalen, Ulleråkersvägen 40 A, Uppsala, 13:15 (Swedish)
Available from: 2013-11-20 Created: 2013-10-26 Last updated: 2014-01-23

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