4.7 Article

Gestational exposure to high fat diets and bisphenol A alters metabolic outcomes in dams and offspring, but produces hepatic steatosis only in dams

Journal

CHEMOSPHERE
Volume 286, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.chemosphere.2021.131645

Keywords

Endocrine disrupting chemicals; Developmental programming; NAFLD; Sexual dimorphism; High-fat diet; Bisphenol-A

Funding

  1. University of Michigan (UM) NIEHS/EPA Children's Environmental Health and Disease Prevention Center [P01 ES022844/RD83543601]
  2. NIEHS [R35 ES031686]
  3. Michigan Lifestage Environmental Exposures and Disease (M-LEEaD) NIEHS Core Center [P30 ES017885]
  4. Rogel Cancer Center [P30 CA046592]
  5. MDRC Chemistry Lab [P30 DK020572]
  6. UM Institutional and Individual Training Grants [T32 ES007062, T32 HD079342, F31 ES025101]

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Perinatal diet and BPA exposure have a greater impact on metabolic outcomes in offspring than on hepatic steatosis. Alterations in dam phenotype by diet and BPA exposure appear to impact offspring health trajectory.
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Perinatal development is a critical window for altered, lifelong health trajectory, and evidence supports the role of perinatal programming in chronic metabolic diseases. To examine the impact of diet and bisphenol A (BPA) on the developmental trajectory of NAFLD in offspring, we exposed dams from pre-gestation through lactation to a human-relevant dose of oral BPA coupled with intake of high fat Western or Mediterranean-style diets. We assessed hepatic steatosis by quantifying hepatic triglycerides (TGs) and metabolic health by measuring body weight, relative organ weights, and serum hormone levels in dams and offspring at postnatal day 10 (PND10) and 10-months of age. In dams, consumption of the Western or Mediterranean diet increased hepatic TGs 1.7-2.4-fold, independent of BPA intake. Among offspring, both perinatal diet and BPA exposure had a greater impact on metabolic outcomes than on hepatic steatosis. At PND10, serum leptin levels were elevated 2.6-4.8-fold in pups exposed to the Mediterranean diet, with a trend for sex-specific effects on body and organ weights. At 10-months, sex-specific increases in organ weight and hormone levels were observed in mice perinatally exposed to Western + BPA or Mediterranean + BPA. These findings suggest lifestage-specific interaction of perinatal exposures to experimental diets and BPA on offspring metabolic health without effects on NAFLD later in life. Importantly, alterations in dam phenotype by diet and BPA exposure appear to impact offspring health trajectory, emphasizing the need to define dam diet in assessing effects of environmental exposures on offspring health.

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