| Title: | Loss of ERalpha partially reverses the effects of maternal high-fat diet on energy homeostasis in female mice |
| Author(s): | Roepke TA; Yasrebi A; Villalobos A; Krumm EA; Yang JA; Mamounis KJ; |
| Address: | "Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. ta.roepke@rutgers.edu. New Jersey Institute for Food, Nutrition, and Health, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. ta.roepke@rutgers.edu. 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. Department of Reproductive Medicine, University of California, San Diego, San Diego, CA 92103, USA. Nutritional Sciences Graduate Program, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA. Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, 32827, USA" |
| DOI: | 10.1038/s41598-017-06560-x |
| ISSN/ISBN: | 2045-2322 (Electronic) 2045-2322 (Linking) |
| Abstract: | "Maternal high-fat diet (HFD) alters hypothalamic developmental programming and disrupts offspring energy homeostasis in rodents. 17beta-estradiol (E2) also influences hypothalamic programming through estrogen receptor (ER) alpha. Therefore, we hypothesized that females lacking ERalpha would be more susceptible to maternal HFD. To address this question, heterozygous ERalpha knockout (WT/KO) dams were fed a control breeder chow diet (25% fat) or a semi-purified HFD (45% fat) 4 weeks prior to mating with WT/KO males or heterozygous males with an ERalpha DNA-binding domain mutation knocked in (WT/KI) to produce WT, ERalpha KO, or ERalpha KIKO females lacking ERE-dependent ERalpha signaling. Maternal HFD increased body weight in WT and KIKO, in part, due to increased adiposity and daytime carbohydrate utilization in WT and KIKO, while increasing nighttime fat utilization in KO. Maternal HFD also increased plasma leptin, IL-6, and MCP-1 in WT and increased arcuate expression of Kiss1 and Esr1 (ERalpha) and liver expression of G6pc and Pepck in WT and KIKO. Contrary to our hypothesis, these data suggest that loss of ERalpha signaling blocks the influence of maternal HFD on energy homeostasis, inflammation, and hypothalamic and liver gene expression and that restoration of ERE-independent ERalpha signaling partially reestablishes susceptibility to maternal HFD" |
| Keywords: | "Animals Body Weight Chemokine CCL2/metabolism Diet, High-Fat/*adverse effects Estradiol/*chemistry/*genetics/metabolism Estrogen Receptor alpha/*chemistry/*genetics/metabolism Female Gene Knockout Techniques Homeostasis Interleukin-6/metabolism Leptin/blo;" |
| Notes: | "MedlineRoepke, Troy A Yasrebi, Ali Villalobos, Alejandra Krumm, Elizabeth A Yang, Jennifer A Mamounis, Kyle J eng P30 ES005022/ES/NIEHS NIH HHS/ R00 DK083457/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. England 2017/07/27 Sci Rep. 2017 Jul 25; 7(1):6381. doi: 10.1038/s41598-017-06560-x" |
