Summary IntroductionThe gastrointestinal (GI) microbiome has emerged as a potential regulator of metabolism. However, the precise mechanisms of how microorganisms may influence physiology remain largely unknown. Interestingly, GI microorganisms, including methanogens, are localized within the same regions as the glucagon-like peptide-1 (GLP-1) secreting L cells. GLP-1 plays key roles appetite and glucose regulation. Furthermore, both methane and GLP-1 levels are altered in obese humans with metabolic disease. We predict that high-fat diet-induced obesity alters the abundance of GI methanogens and that methane may play a role in the GLP-1 secretory response from the L cell. MethodsTo demonstrate this, GLP-1 secretion response and faecal methanogens were examined in mice given a high-fat diet for 14?weeks. In addition, the direct effect of methane on GLP-1 secretion was assessed in two L-cell models (NCI-H716 and GLUTag). ResultsHigh-fat diet caused a significant increase in both GLP-1 secretion and faecal methanogen content. There was a direct correlation between GLP-1 secretion response and faecal methanogen levels. In L cells, methane stimulated GLP-1 secretion and enhanced intracellular cAMP content. ConclusionThese results indicate that alterations in the methanogen communities occurring in obesity may play a vital role in directly enhancing GLP-1 secretion, and that methane can directly stimulate the secretion of GLP-1.
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