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.
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.


OBJECTIVE
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.
La Merrill
Michele
M
Department of Genetics, Center for Environmental Health and Susceptibility, University of North Carolina at Chapel Hill, Chapel Hill, NC 27695, USA.
Kuruvilla
Bittu S
BS
Pomp
Daniel
D
Birnbaum
Linda S
LS
Threadgill
David W
DW
D000818:Animals; D001823:Body Composition; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004041:Dietary Fats / Q000008:administration & dosage*; D004790:Enzyme Induction; D005260:Female; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000378:metabolism; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
D004041:Dietary Fats; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D003577:Cytochrome P-450 Enzyme System