Source:Cell Reports
Author(s): Maria Mavilio, Valentina Marchetti, Marta Fabrizi, Robert Stöhr, Arianna Marino, Viviana Casagrande, Loredana Fiorentino, Marina Cardellini, Ben Kappel, Ivan Monteleone, Celine Garret, Alessandro Mauriello, Giovanni Monteleone, Alessio Farcomeni, Remy Burcelin, Rossella Menghini, Massimo Federici
The effect of gut microbiota on obesity and insulin resistance is now recognized, but the underlying host-dependent mechanisms remain poorly undefined. We find that tissue inhibitor of metalloproteinase 3 knockout (Timp3−/−) mice fed a high-fat diet exhibit gut microbiota dysbiosis, an increase in branched chain and aromatic (BCAA) metabolites, liver steatosis, and an increase in circulating soluble IL-6 receptors (sIL6Rs). sIL6Rs can then activate inflammatory cells, such as CD11c+ cells, which drive metabolic inflammation. Depleting the microbiota through antibiotic treatment significantly improves glucose tolerance, hepatic steatosis, and systemic inflammation, and neutralizing sIL6R signaling reduces inflammation, but only mildly impacts glucose tolerance. Collectively, our results suggest that gut microbiota is the primary driver of the observed metabolic dysfunction, which is mediated, in part, through IL-6 signaling. Our findings also identify an important role for Timp3 in mediating the effect of the microbiota in metabolic diseases.
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Mavilio et al. show that Timp3 impacts gut-microbiome-related liver steatosis and glucose intolerance. Loss of Timp3 potentiates gut microbiota dysbiosis, leading to an increase in the development of inflammatory and metabolic abnormalities, which are mediated, in part, through IL-6 signaling. Antibiotic-mediated depletion of the microbiota improved these metabolic and inflammatory phenotypes.from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/297Npnq
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