| Title: | The loss of ERE-dependent ERalpha signaling potentiates the effects of maternal high-fat diet on energy homeostasis in female offspring fed an obesogenic diet |
| 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. 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" |
| DOI: | 10.1017/S2040174419000515 |
| ISSN/ISBN: | 2040-1752 (Electronic) 2040-1744 (Print) 2040-1744 (Linking) |
| Abstract: | "Maternal high-fat diet (HFD) alters hypothalamic programming and disrupts offspring energy homeostasis in rodents. We previously reported that the loss of ERalpha 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 ERalpha 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, ERalpha KO, or ERalpha 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 alpha 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 ERalpha signaling, and not total ERalpha 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 ERalpha signaling" |
| Keywords: | "Animals Diet, High-Fat/*adverse effects Disease Models, Animal Energy Metabolism/*genetics Estrogen Receptor alpha/genetics/*metabolism Female *Gene Expression Regulation, Developmental Gene Knock-In Techniques Genetic Predisposition to Disease Humans Inf;" |
| 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/ R21 ES027119/ES/NIEHS NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. England 2019/09/24 J Dev Orig Health Dis. 2020 Jun; 11(3):285-296. doi: 10.1017/S2040174419000515. Epub 2019 Sep 23" |
