دورية أكاديمية
Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation.
| العنوان: | Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation. |
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| المؤلفون: | Jones, Nicholas, Blagih, Julianna, Zani, Fabio, Rees, April, Hill, David G, Jenkins, Benjamin J, Bull, Caroline J, Moreira, Diana, Bantan, Azari I M, Cronin, James G, Avancini, Daniele, Jones, Gareth W, Finlay, David K, Vousden, Karen H, Vincent, Emma E, Thornton, Catherine A |
| المصدر: | Nature communications ; 12 ; 1 ; 1209 ; United Kingdom ; Canada ; England |
| سنة النشر: | 2021 |
| المجموعة: | Lenus - Irish Health Publications Archive (HSE - Health Service Executive) |
| مصطلحات موضوعية: | DIABETES MELLITUS, IMMUNOLOGY, METABOLISM |
| الوصف: | Fructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-1723 |
| العلاقة: | http://hdl.handle.net/10147/631975Test; Nature communications |
| DOI: | 10.1038/s41467-021-21461-4 |
| الإتاحة: | https://doi.org/10.1038/s41467-021-21461-4Test http://hdl.handle.net/10147/631975Test |
| رقم الانضمام: | edsbas.8D50CF6F |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/s41467-021-21461-4 |