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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

Schematic of treatment groups (A) and time line (B). Impregnated B6 and D2 iparous mice were treated with 1 μg/μL TCDD or 95%/5% olive oil/toluene (vehicle) at 12.5dpc. Dams received HFD or LFD at parturition, and pups were weaned onto the same diets.
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f1-ehp-117-1414: Schematic of treatment groups (A) and time line (B). Impregnated B6 and D2 iparous mice were treated with 1 μg/μL TCDD or 95%/5% olive oil/toluene (vehicle) at 12.5dpc. Dams received HFD or LFD at parturition, and pups were weaned onto the same diets.

Mentions: B6 and D2 iparous female mice (Jackson Laboratory, Bar Harbor, ME) were mated with B6 and D2 males, respectively, and dosed with 1 μg/kg TCDD or vehicle control by oral gavage at 12.5 days postcoitus (dpc), corresponding to the time when fetal mammary fat pads are developing (n = 24 dams per strain and treatment group). On postnatal day (PND) 0, dams were changed from 5058 chow (Purina, St. Louis, MO) to an HFD (45% total kilocalories from fat and 35% total kilocalories from carbohydrate; D12451, Research Diets, New Brunswick, NJ; n = 12 dams) or a matched control low-fat diet (LFD; 10% total kilocalories from fat and 70% kilocalories from carbohydrate; D12450B, Research Diets; n = 12 dams) (Figure 1). Diets had the same percentage of protein, with fat differences being achieved through increased maltodextrin and lard and decreased cornstarch and sucrose in HFD compared with LFD (400, 1,598, 291, and 691 kcal vs. 140, 180, 1,260, and 1,400 kcal, respectively). The LFD has fat levels that fall into the range often found in standard rodent chows. Mice had ad libitum access to feed and water. Female pups were weaned at PND21, ending any lactational exposure to TCDD but continuing their respective HFD or LFD exposures. Female D2 offspring were dosed with 60 mg/kg DMBA (n = 12 litters) or vehicle (n = 12 litters) by oral gavage on PND35, when developing pubertal mammary glands are known to be sensitive to DMBA exposure. Mice were euthanized 24 hr later by carbon dioxide asphyxiation. All animal experiments were performed humanely using protocols to alleviate suffering and were approved by the University of North Carolina at Chapel Hill Institutional Animal Care and Use Committee and were performed in a vivarium accredited by the Association for Assessment and Accreditation of Laboratory Animal Care. Because survival of B6 offspring was greatly reduced in the HFD group treated with TCDD, B6 offspring were not analyzed further.


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)

Schematic of treatment groups (A) and time line (B). Impregnated B6 and D2 iparous mice were treated with 1 μg/μL TCDD or 95%/5% olive oil/toluene (vehicle) at 12.5dpc. Dams received HFD or LFD at parturition, and pups were weaned onto the same diets.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f1-ehp-117-1414: Schematic of treatment groups (A) and time line (B). Impregnated B6 and D2 iparous mice were treated with 1 μg/μL TCDD or 95%/5% olive oil/toluene (vehicle) at 12.5dpc. Dams received HFD or LFD at parturition, and pups were weaned onto the same diets.
Mentions: B6 and D2 iparous female mice (Jackson Laboratory, Bar Harbor, ME) were mated with B6 and D2 males, respectively, and dosed with 1 μg/kg TCDD or vehicle control by oral gavage at 12.5 days postcoitus (dpc), corresponding to the time when fetal mammary fat pads are developing (n = 24 dams per strain and treatment group). On postnatal day (PND) 0, dams were changed from 5058 chow (Purina, St. Louis, MO) to an HFD (45% total kilocalories from fat and 35% total kilocalories from carbohydrate; D12451, Research Diets, New Brunswick, NJ; n = 12 dams) or a matched control low-fat diet (LFD; 10% total kilocalories from fat and 70% kilocalories from carbohydrate; D12450B, Research Diets; n = 12 dams) (Figure 1). Diets had the same percentage of protein, with fat differences being achieved through increased maltodextrin and lard and decreased cornstarch and sucrose in HFD compared with LFD (400, 1,598, 291, and 691 kcal vs. 140, 180, 1,260, and 1,400 kcal, respectively). The LFD has fat levels that fall into the range often found in standard rodent chows. Mice had ad libitum access to feed and water. Female pups were weaned at PND21, ending any lactational exposure to TCDD but continuing their respective HFD or LFD exposures. Female D2 offspring were dosed with 60 mg/kg DMBA (n = 12 litters) or vehicle (n = 12 litters) by oral gavage on PND35, when developing pubertal mammary glands are known to be sensitive to DMBA exposure. Mice were euthanized 24 hr later by carbon dioxide asphyxiation. All animal experiments were performed humanely using protocols to alleviate suffering and were approved by the University of North Carolina at Chapel Hill Institutional Animal Care and Use Committee and were performed in a vivarium accredited by the Association for Assessment and Accreditation of Laboratory Animal Care. Because survival of B6 offspring was greatly reduced in the HFD group treated with TCDD, B6 offspring were not analyzed further.

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