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Dietary fat alters body composition, mammary development, and cytochrome p450 induction after maternal TCDD exposure in DBA/2J mice with low-responsive aryl hydrocarbon receptors.

La Merrill M, Kuruvilla BS, Pomp D, Birnbaum LS, Threadgill DW - Environ. Health Perspect. (2009)

Bottom Line: Maternal TCDD exposure resulted in reduced litter size in D2 mice and, on HFD, reduced postpartum survival in B6 mice.In D2 mice, HFD increased body mass and fat in off-spring, induced precocious mammary gland development, and increased AHR expression compared with mice given an LFD.We conclude that despite having a low-responsive AHR, D2 progeny fed a diet similar to that consumed by most people are susceptible to TCDD and DMBA exposure effects blood glucose levels, mammary differentiation, and hepatic Cyp1 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, Chapel Hill, NC 27695, USA.

ABSTRACT

Background: Increased fat intake is associated with obesity and may make obese individuals uniquely susceptible to the effects of lipophilic aryl hydrocarbon receptor (AHR) ligands.

Objectives: We investigated the consequences of high-fat diet (HFD) and AHR ligands on body composition, mammary development, and hepatic P450 expression.

Methods: Pregnant C57BL/6J (B6) and DBA/2J (D2) dams, respectively expressing high- or low-responsive AHR, were dosed at mid-gestation with TCDD. At parturition, mice were placed on an HFD or a low-fat diet (LFD). Body fat of progeny was measured before dosing with 7,12-dimethylbenz[a]anthracene (DMBA). Fasting blood glucose was measured, and liver and mammary glands were analyzed.

Results: Maternal TCDD exposure resulted in reduced litter size in D2 mice and, on HFD, reduced postpartum survival in B6 mice. In D2 mice, HFD increased body mass and fat in off-spring, induced precocious mammary gland development, and increased AHR expression compared with mice given an LFD. Maternal TCDD exposure increased hepatic Cyp1a1 and Cyp1b1 expression in offspring on both diets, but DMBA depressed Cyp1b1 expression only in mice fed an HFD. In D2 progeny, TCDD exposure decreased mammary terminal end bud size, and DMBA exposure decreased the number of terminal end buds. Only in D2 progeny fed HFD did perinatal TCDD increase blood glucose and the size of mammary fat pads, while decreasing both branch elongation and the number of terminal end buds.

Conclusions: We conclude that despite having a low-responsive AHR, D2 progeny fed a diet similar to that consumed by most people are susceptible to TCDD and DMBA exposure effects blood glucose levels, mammary differentiation, and hepatic Cyp1 expression.

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Related in: MedlinePlus

Maternal TCDD exposure and effect of diet on gene expression. Normalized message levels are represented as mean ± SE. (A) Induction of Cyp1a1 was increased by TCDD exposure compared with vehicle (n = 11 and 10 litters, respectively). Measurements were pooled across diet and DMBA groups. (B ) Induction of Cyp1b1 was increased by TCDD compared with vehicle (n = 11 and 10 litters, respectively). Measurements were pooled across diet and DMBA groups. (C) Induction of Ahr was increased by HFD relative to LFD (n = 11 and 10 litters, respectively). Measurements were pooled across TCDD and DMBA groups. (D) Induction of Cyp1b1 by DMBA was decreased compared with vehicle in HFD-fed but not in LFD-fed D2 mice. LFD groups are vehicle (n = 5 litters) and DMBA (n = 5 litters); HFD groups are vehicle (n = 6 litters) and DMBA (n = 5 litters).*p < 0.05.
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f5-ehp-117-1414: Maternal TCDD exposure and effect of diet on gene expression. Normalized message levels are represented as mean ± SE. (A) Induction of Cyp1a1 was increased by TCDD exposure compared with vehicle (n = 11 and 10 litters, respectively). Measurements were pooled across diet and DMBA groups. (B ) Induction of Cyp1b1 was increased by TCDD compared with vehicle (n = 11 and 10 litters, respectively). Measurements were pooled across diet and DMBA groups. (C) Induction of Ahr was increased by HFD relative to LFD (n = 11 and 10 litters, respectively). Measurements were pooled across TCDD and DMBA groups. (D) Induction of Cyp1b1 by DMBA was decreased compared with vehicle in HFD-fed but not in LFD-fed D2 mice. LFD groups are vehicle (n = 5 litters) and DMBA (n = 5 litters); HFD groups are vehicle (n = 6 litters) and DMBA (n = 5 litters).*p < 0.05.

Mentions: Maternal TCDD exposure increased hepatic Cyp1a1 and Cyp1b1 expression at puberty in D2 female progeny relative to vehicle exposure, independent of diet (p < 0.01; Figure 5A,B), whereas only HFD increased hepatic Ahr expression significantly compared with LFD at the same time point irrespective of TCDD exposure (p < 0.05; Figure 5C). Although DMBA and diet had no significant main additive effect on hepatic Cyp1b1 expression, their interaction term was significant in the generalized linear model for hepatic Cyp1b1 expression; when D2 female mice were maintained on HFD, DMBA induction of hepatic Cyp1b1 expression was significantly reduced in progeny from the maternally exposed TCDD group relative to the maternal vehicle controls (p < 0.05; Figure 5D). When D2 female progeny were maintained on LFD, maternal TCDD exposure had no effect on hepatic Cyp1b1 induction after DMBA exposure.


Dietary fat alters body composition, mammary development, and cytochrome p450 induction after maternal TCDD exposure in DBA/2J mice with low-responsive aryl hydrocarbon receptors.

La Merrill M, Kuruvilla BS, Pomp D, Birnbaum LS, Threadgill DW - Environ. Health Perspect. (2009)

Maternal TCDD exposure and effect of diet on gene expression. Normalized message levels are represented as mean ± SE. (A) Induction of Cyp1a1 was increased by TCDD exposure compared with vehicle (n = 11 and 10 litters, respectively). Measurements were pooled across diet and DMBA groups. (B ) Induction of Cyp1b1 was increased by TCDD compared with vehicle (n = 11 and 10 litters, respectively). Measurements were pooled across diet and DMBA groups. (C) Induction of Ahr was increased by HFD relative to LFD (n = 11 and 10 litters, respectively). Measurements were pooled across TCDD and DMBA groups. (D) Induction of Cyp1b1 by DMBA was decreased compared with vehicle in HFD-fed but not in LFD-fed D2 mice. LFD groups are vehicle (n = 5 litters) and DMBA (n = 5 litters); HFD groups are vehicle (n = 6 litters) and DMBA (n = 5 litters).*p < 0.05.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2737019&req=5

f5-ehp-117-1414: Maternal TCDD exposure and effect of diet on gene expression. Normalized message levels are represented as mean ± SE. (A) Induction of Cyp1a1 was increased by TCDD exposure compared with vehicle (n = 11 and 10 litters, respectively). Measurements were pooled across diet and DMBA groups. (B ) Induction of Cyp1b1 was increased by TCDD compared with vehicle (n = 11 and 10 litters, respectively). Measurements were pooled across diet and DMBA groups. (C) Induction of Ahr was increased by HFD relative to LFD (n = 11 and 10 litters, respectively). Measurements were pooled across TCDD and DMBA groups. (D) Induction of Cyp1b1 by DMBA was decreased compared with vehicle in HFD-fed but not in LFD-fed D2 mice. LFD groups are vehicle (n = 5 litters) and DMBA (n = 5 litters); HFD groups are vehicle (n = 6 litters) and DMBA (n = 5 litters).*p < 0.05.
Mentions: Maternal TCDD exposure increased hepatic Cyp1a1 and Cyp1b1 expression at puberty in D2 female progeny relative to vehicle exposure, independent of diet (p < 0.01; Figure 5A,B), whereas only HFD increased hepatic Ahr expression significantly compared with LFD at the same time point irrespective of TCDD exposure (p < 0.05; Figure 5C). Although DMBA and diet had no significant main additive effect on hepatic Cyp1b1 expression, their interaction term was significant in the generalized linear model for hepatic Cyp1b1 expression; when D2 female mice were maintained on HFD, DMBA induction of hepatic Cyp1b1 expression was significantly reduced in progeny from the maternally exposed TCDD group relative to the maternal vehicle controls (p < 0.05; Figure 5D). When D2 female progeny were maintained on LFD, maternal TCDD exposure had no effect on hepatic Cyp1b1 induction after DMBA exposure.

Bottom Line: Maternal TCDD exposure resulted in reduced litter size in D2 mice and, on HFD, reduced postpartum survival in B6 mice.In D2 mice, HFD increased body mass and fat in off-spring, induced precocious mammary gland development, and increased AHR expression compared with mice given an LFD.We conclude that despite having a low-responsive AHR, D2 progeny fed a diet similar to that consumed by most people are susceptible to TCDD and DMBA exposure effects blood glucose levels, mammary differentiation, and hepatic Cyp1 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, Chapel Hill, NC 27695, USA.

ABSTRACT

Background: Increased fat intake is associated with obesity and may make obese individuals uniquely susceptible to the effects of lipophilic aryl hydrocarbon receptor (AHR) ligands.

Objectives: We investigated the consequences of high-fat diet (HFD) and AHR ligands on body composition, mammary development, and hepatic P450 expression.

Methods: Pregnant C57BL/6J (B6) and DBA/2J (D2) dams, respectively expressing high- or low-responsive AHR, were dosed at mid-gestation with TCDD. At parturition, mice were placed on an HFD or a low-fat diet (LFD). Body fat of progeny was measured before dosing with 7,12-dimethylbenz[a]anthracene (DMBA). Fasting blood glucose was measured, and liver and mammary glands were analyzed.

Results: Maternal TCDD exposure resulted in reduced litter size in D2 mice and, on HFD, reduced postpartum survival in B6 mice. In D2 mice, HFD increased body mass and fat in off-spring, induced precocious mammary gland development, and increased AHR expression compared with mice given an LFD. Maternal TCDD exposure increased hepatic Cyp1a1 and Cyp1b1 expression in offspring on both diets, but DMBA depressed Cyp1b1 expression only in mice fed an HFD. In D2 progeny, TCDD exposure decreased mammary terminal end bud size, and DMBA exposure decreased the number of terminal end buds. Only in D2 progeny fed HFD did perinatal TCDD increase blood glucose and the size of mammary fat pads, while decreasing both branch elongation and the number of terminal end buds.

Conclusions: We conclude that despite having a low-responsive AHR, D2 progeny fed a diet similar to that consumed by most people are susceptible to TCDD and DMBA exposure effects blood glucose levels, mammary differentiation, and hepatic Cyp1 expression.

Show MeSH
Related in: MedlinePlus