論文 - 詳細
| RRC ID | 87290 |
|---|---|
| 著者 | Abi-Ghanem C, Salinero AE, Smith RM, Kelly RD, Belanger KM, Richard RN, Paul AS, Herzog AA, Thrasher CA, Rybka KA, Riccio D, Gannon OJ, Kordit D, Kyaw NR, Mansour FM, Groom E, Brooks HL, Robison LS, Pumiglia K, Zuloaga DG, Zuloaga KL. |
| タイトル | Effects of Menopause and High Fat Diet on Metabolic Outcomes in a Mouse Model of Alzheimer's Disease. |
| ジャーナル | J Alzheimers Dis |
| Abstract |
BACKGROUND:About two-thirds of those with Alzheimer's disease (AD) are women, most of whom are post-menopausal. Menopause accelerates dementia risk by increasing the risk for metabolic, cardiovascular, and cerebrovascular diseases. Mid-life metabolic disease (obesity, diabetes/prediabetes) is a well-known risk factor for dementia. A high fat diet can lead to poor metabolic health in both humans and rodents. OBJECTIVE:Our goal was to determine the effects of a high fat diet on metabolic outcomes in the AppNL-F knock-in mouse model of AD and assess the effects of menopause. METHODS:First, 3-month-old AppNL-F and WT female mice were placed on either a control or a high fat diet until 10 months of age then assessed for metabolic outcomes. Next, we did a more extensive assessment in AppNL-F mice that were administered VCD (4-vinylcyclohexene diepoxide) or vehicle (oil) and placed on a control or high fat diet for 7 months. VCD was used to model menopause by causing accelerated ovarian failure. RESULTS:Compared to WT controls, AD female mice had worse glucose intolerance. Menopause led to metabolic impairment (weight gain and glucose intolerance) and further exacerbated obesity in response to a high fat diet. There were interactions between diet and menopause on some metabolic health serum biomarkers and the expression of hypothalamic markers related to energy balance. CONCLUSIONS:This work highlights the need to model endocrine aging in animal models of dementia and will contribute to further understanding the interaction between menopause and metabolic health in the context of AD. |
| 巻・号 | 101(4) |
| ページ | 1177-1194 |
| 公開日 | 2024-1-1 |
| DOI | 10.3233/JAD-231332 |
| PII | JAD231332 |
| PMID | 39302361 |
| PMC | PMC12045035 |
| MeSH | Alzheimer Disease* / metabolism Amyloid beta-Protein Precursor / genetics Amyloid beta-Protein Precursor / metabolism Animals Cyclohexenes Diet, High-Fat* / adverse effects Disease Models, Animal* Female Menopause* / metabolism Mice Mice, Inbred C57BL Mice, Transgenic* Obesity / metabolism Vinyl Compounds |
| リソース情報 | |
| 実験動物マウス | RBRC06343 |