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The loss of ERE-dependent ERα signaling potentiates the effects of maternal high-fat diet on energy homeostasis in female offspring fed an obesogenic diet

Published online by Cambridge University Press:  23 September 2019

Troy A. Roepke Open the ORCID record for Troy A. Roepke [Opens in a new window] ,
Ali Yasrebi ,
Alejandra Villalobos ,
Elizabeth A. Krumm ,
Jennifer A. Yang  and
Kyle J. Mamounis
Troy A. Roepke*
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Nutritional Sciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA New Jersey Institute for Food, Nutrition, and Health, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Ali Yasrebi
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Alejandra Villalobos
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Elizabeth A. Krumm
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Jennifer A. Yang
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Graduate Program in Endocrinology and Animal Biosciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
Kyle J. Mamounis
Affiliation:
Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA Nutritional Sciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
*
Address for correspondence: Troy A. Roepke, Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, 84 Lipman Drive, Bartlett Hall, New Brunswick, NJ 08901, USA. Email: [email protected]
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Abstract

Maternal high-fat diet (HFD) alters hypothalamic programming and disrupts offspring energy homeostasis in rodents. We previously reported that the loss of ERα signaling partially blocks the effects of maternal HFD in female offspring fed a standard chow diet. In a companion study, we determined if the effects of maternal HFD were magnified by an adult obesogenic diet in our transgenic mouse models. Heterozygous ERα knockout (wild-type (WT)/KO) dams were fed a control breeder chow diet (25% fat) or a semipurified HFD (45% fat) 4 weeks prior to mating with heterozygous males (WT/KO or WT/ knockin) to produce WT, ERα KO, or ERα knockin/knockout (KIKO) (no estrogen response element (ERE) binding) female offspring, which were fed HFD for 20 weeks. Maternal HFD potentiated the effects of adult HFD on KIKO and KO body weight due to increased adiposity and decreased activity. Maternal HFD also produced KIKO females that exhibit KO-like insulin intolerance and impaired glucose homeostasis. Maternal HFD increased plasma interleukin 6 and monocyte chemoattractant protein 1 levels and G6pc and Pepck liver expression only in WT mice. Insulin and tumor necrosis factor α levels were higher in KO offspring from HFD-fed dams. Arcuate and liver expression of Esr1 was altered in KIKO and WT, respectively. These data suggest that loss of ERE-dependent ERα signaling, and not total ERα signaling, sensitizes females to the deleterious influence of maternal HFD on offspring energy and glucose potentially through the control of peripheral inflammation and hypothalamic and liver gene expression. Future studies will interrogate the tissue-specific mechanisms of maternal HFD programming through ERα signaling.

Keywords

Estrogen receptor αenergy homeostasisglucose homeostasisarcuate nucleusobesity
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 3 , June 2020 , pp. 285 - 296
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2019

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Footnotes

Current address: Jennifer A. Yang, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Diego, San Diego, CA 92103, USA.

Kyle J. Mamounis, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.

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