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Environmental Contaminants and Obesity
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 949
Keyword [en]
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
Identifiers
URN: urn:nbn:se:uu:diva-209807ISBN: 978-91-554-8798-0 (print)OAI: oai:DiVA.org:uu-209807DiVA: diva2:659846
Public defence
2013-12-13, Frödingsalen, Ulleråkersvägen 40 A, Uppsala, 13:15 (Swedish)
Opponent
Supervisors
Available from: 2013-11-20 Created: 2013-10-26 Last updated: 2016-11-04
List of papers
1. Quantification of total and visceral adipose tissue in fructose-fed rats using water-fat separated single echo MRI
Open this publication in new window or tab >>Quantification of total and visceral adipose tissue in fructose-fed rats using water-fat separated single echo MRI
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2013 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 21, no 9, E388-E395 p.Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of this study was to setup a rodent model for modest weight gain and an MRI-based quantification of body composition on a clinical 1.5 T MRI system for studies of obesity and environmental factors and their possible association. Design and Methods: Twenty-four 4-week-old female Fischer rats were divided into two groups: one exposed group (n=12) and one control group (n 12). The exposed group was given drinking water containing fructose (5% for 7 weeks, then 20% for 3 weeks). The control group was given tap water. Before sacrifice, whole body MRI was performed to determine volumes of total and visceral adipose tissue and lean tissue. MRI was performed using a clinical 1.5 T system and a chemical shift based technique for separation of water and fat signal from a rapid single echo acquisition. Fat signal fraction was used to separate adipose and lean tissue. Visceral adipose tissue volume was quantified using semiautomated segmentation. After sacrifice, a perirenal fat pad and the liver were dissected and weighed. Plasma proteins were analyzed by Western blot. Results: The weight gain was 5.2% greater in rats exposed to fructose than in controls (P=0.042). Total and visceral adipose tissue volumes were 5.2 cm(3) (P=0.017) and 3.1 cm(3) (P=0.019) greater, respectively, while lean tissue volumes did not differ. The level of triglycerides and apolipoprotein A-I was higher (P=0.034, P=0.005, respectively) in fructose-exposed rats.

National Category
Medical Image Processing Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-209508 (URN)10.1002/oby.20229 (DOI)000325426600007 ()
Available from: 2013-10-21 Created: 2013-10-21 Last updated: 2017-12-06Bibliographically approved
2. Bisphenol A exposure increases liver fat in juvenile fructose-fed Fischer 344 rats
Open this publication in new window or tab >>Bisphenol A exposure increases liver fat in juvenile fructose-fed Fischer 344 rats
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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]

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSION:

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.

Keyword
MRI, Liver fat, Rat, Bisphenol A, Obesity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-185549 (URN)10.1016/j.tox.2012.09.013 (DOI)000314856800014 ()23142792 (PubMedID)
Available from: 2012-11-08 Created: 2012-11-26 Last updated: 2017-12-07Bibliographically approved
3. Circulating levels of persistent organic pollutants associate in divergent ways to fat mass measured by DXA in humans
Open this publication in new window or tab >>Circulating levels of persistent organic pollutants associate in divergent ways to fat mass measured by DXA in humans
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2011 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 85, no 3, 335-343 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Environmental contaminants have recently been implicated in the pathogenesis of obesity.

OBJECTIVE:

To explore relations between persistent organic pollutants (POPs) and fat mass independently of body stature, using a cross-sectional design.

METHODS:

In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS), fat mass was determined in 70-year-old subjects (n=890) by dual-energy X-ray absorptiometry (DXA). The plasma levels of 21 POPs (including 16 PCB congeners, 3 OC pesticides, 1 BDE47, and 1 dioxin) were measured by high resolution chromatography coupled with high resolution mass spectrometry (HRGC/HRMS).

RESULTS:

Lipid-standardized plasma concentrations of octachlorodibenzo-p-dioxin (OCDD), the PCBs 74, 99, 105 and 118, and the pesticides HCB, TNK, and DDE were all positively related to fat mass (p=0.03-0.0001). Subjects in the fifth quintile for PCB 105 showed a mean fat mass that was 4.8kg more than subjects in the first quintile. On the other hand, the PCBs 156, 157, 169, 170, 180, 189, 194, 206, and 209 were negatively related to fat mass (p=0.0001). For PCB 194, subjects in the fifth quintile showed a mean fat mass that was 10.8kg less than subjects in the first quintile. Following adjustment for smoking, physical activity, education level, height, lean mass, and gender, these results remained significant (p=0.01-0.0001) except for the PCBs 74 and 99. For some PCBs, the associations vs. fat mass were more pronounced in women than in men.

CONCLUSION:

Plasma concentrations of some pesticides are positively related to fat mass, while divergent associations are seen for the PCBs. These results implicate a complex role of POPs in obesity.

Keyword
DXA, Dioxin, Fat mass, Obesity, Persistent organic pollutants (POPs), Pesticides
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-161503 (URN)10.1016/j.chemosphere.2011.06.095 (DOI)000297661900007 ()21767864 (PubMedID)
Available from: 2011-11-14 Created: 2011-11-14 Last updated: 2017-12-08Bibliographically approved
4. Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans
Open this publication in new window or tab >>Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans
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2014 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 112, 42-48 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Since bisphenol A (BPA) has been shown to induce obesity in experimental studies, we explored the associations between BPA and fat mass, fat distribution and circulating levels of adiponectin, leptin and ghrelin in humans.

METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), fat mass and fat distribution were determined in 70-year-old men and women (n=890) by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) (n=287). Serum levels of BPA were analyzed using isotope liquid chromatography/tandem mass spectrometer (API4000LC-MS/MS). Hormone levels were analyzed with radioimmunoassays (RIA) or enzyme-linked immunosorbent assay (ELISA). Imaging was performed approximately two years following collection of other data.

RESULTS: Serum concentrations of BPA were not related to adipose tissue measurements by DXA or MRI. BPA associated positively with adiponectin and leptin, but negatively with ghrelin, following adjustments for sex, height, fat mass, lean mass, smoking, alcohol consumption, physical activity, energy intake, and educational levels (p<0.001, p=0.009, p<0.001, respectively). The relationship between BPA and ghrelin was stronger in women than in men.

CONCLUSION: Although no relationships between BPA levels and measures of fat mass were seen, BPA associated strongly with the adipokines adiponectin and leptin and with the gut-hormone ghrelin suggesting that BPA may interfere with hormonal control of hunger and satiety.

Keyword
BPA; Adiponectin; Leptin; Ghrelin; Adipose tissue
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-229030 (URN)10.1016/j.chemosphere.2014.03.042 (DOI)000340688300006 ()25048886 (PubMedID)
Funder
Swedish Research CouncilSwedish Research Council Formas
Note

Correction in Chemosphere, 2015, vol 139, pp. 1, DOI: 10.1016/j.chemosphere.2015.05.050

Available from: 2014-07-27 Created: 2014-07-27 Last updated: 2017-12-05Bibliographically approved

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