Nature communications, 2021-02, Vol.12 (1), p.1209-13, Article 1209
2021
Details
- Autor(en) / Beteiligte
- Titel
- Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation
- Ist Teil von
- Nature communications, 2021-02, Vol.12 (1), p.1209-13, Article 1209
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-21461-4Titel-ID: cdi_doaj_primary_oai_doaj_org_article_e704cf7cb7a0484a9ad0d96a44d08b6a
- Format
- –
- Schlagworte
- Acids - metabolism, Animals, Citric Acid Cycle - drug effects, Cytokines, Cytokines - metabolism, Diabetes mellitus (non-insulin dependent), Diet, Disease Models, Animal, Exposure, Fatty liver, Flexibility, Fructose, Fructose - pharmacology, Glucose - pharmacology, Glutamine, Glutamine - metabolism, Glycolysis, Glycolysis - drug effects, IL-1β, Immune system, Inflammation, Inflammation - metabolism, Inflammation - pathology, Isotope Labeling, Leukocytes (mononuclear), Lipopolysaccharides, Lipopolysaccharides - toxicity, Liver diseases, Macrophages, Macrophages - drug effects, Macrophages - metabolism, Metabolic Flux Analysis, Metabolic pathways, Metabolism, Mice, Mice, Inbred C57BL, Mitochondria, Mitochondria - drug effects, Mitochondria - pathology, Monocytes, Monocytes - drug effects, Monocytes - metabolism, Monosaccharides, Myeloid cells, Oxidation-Reduction, Oxidative metabolism, Oxidative Phosphorylation - drug effects, Oxygen Consumption - drug effects, Phagocytes, Phenotype, Phenotypes, T-Lymphocytes - drug effects, T-Lymphocytes - metabolism