| First Author | Roepke TA | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 6381 |
| PubMed ID | 28743985 | Mgi Jnum | J:250194 |
| Mgi Id | MGI:5926929 | Doi | 10.1038/s41598-017-06560-x |
| Citation | Roepke TA, et al. (2017) Loss of ERalpha partially reverses the effects of maternal high-fat diet on energy homeostasis in female mice. Sci Rep 7(1):6381 |
| abstractText | 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. |
