Non-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive Impairment in High-Fat Diet-induced Obese Mice
| العنوان: | Non-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive Impairment in High-Fat Diet-induced Obese Mice |
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| المؤلفون: | Paul R. Blakemore, John A. Katzenellenbogen, Cristobal L. Miranda, Gerd Bobe, Lance A. Johnson, Adrian F. Gombart, Benita S. Katzenellenbogen, Ines L. Paraiso, Valerie Elias, Jacob Raber, Jan F. Stevens, Urszula T. Iwaniec, Claudia S. Maier, Johana S Revel, Ralph L. Reed, Lea S. Ullrich, Joshua J. Hay, Russell T. Turner, Chrissa Kioussi, Oriane de Montgolfier, Jaewoo Choi |
| المصدر: | Scientific Reports, Vol 8, Iss 1, Pp 1-17 (2018) Scientific Reports |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Metabolite, Spatial Learning, lcsh:Medicine, Estrogen receptor, Diet, High-Fat, Article, Cell Line, Impaired glucose tolerance, Mice, Plasma, 03 medical and health sciences, chemistry.chemical_compound, Insulin resistance, Internal medicine, medicine, Animals, Humans, Cognitive Dysfunction, Obesity, lcsh:Science, Spatial Memory, Flavonoids, Metabolic Syndrome, Liver injury, Propiophenones, Multidisciplinary, Muscles, Leptin, lcsh:R, Lipid metabolism, medicine.disease, 3. Good health, Disease Models, Animal, 030104 developmental biology, Endocrinology, Liver, chemistry, Flavanones, Xanthohumol, MCF-7 Cells, lcsh:Q |
| الوصف: | Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional glucose and lipid metabolism in animal models of metabolic syndrome (MetS). However, its metabolic transformation into the estrogenic metabolite, 8-prenylnaringenin (8-PN), poses a potential health concern for its use in humans. To address this concern, we evaluated two hydrogenated derivatives, α,β-dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for estrogen receptors α and β, and which cannot be metabolically converted into 8-PN. We compared their effects to those of XN by feeding C57BL/6J mice a high-fat diet (HFD) containing XN, DXN, or TXN for 13 weeks. DXN and TXN were present at higher concentrations than XN in plasma, liver and muscle. Mice administered XN, DXN or TXN showed improvements of impaired glucose tolerance compared to the controls. DXN and TXN treatment resulted in a decrease of HOMA-IR and plasma leptin. C2C12 embryonic muscle cells treated with DXN or TXN exhibited higher rates of uncoupled mitochondrial respiration compared to XN and the control. Finally, XN, DXN, or TXN treatment ameliorated HFD-induced deficits in spatial learning and memory. Taken together, DXN and TXN could ameliorate the neurocognitive-metabolic impairments associated with HFD-induced obesity without risk of liver injury and adverse estrogenic effects. |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::60d0ee980eb4bc73577ea29330f0672b https://doi.org/10.1038/s41598-017-18992-6 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....60d0ee980eb4bc73577ea29330f0672b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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