Background: Obesity is a risk factor in the development of a variety of diseases including cardiovascular disease and type 2 diabetes. Circulating fatty acids (including palmitate) and protein glycation are both increased in obesity and diabetes and are known to cause metabolic stress. This includes the impairment of the glucoregulatory hormone glucagon-like peptide-1 (GLP-1) secreted from intestinal L-cells. Recently, the gastrointestinal microbiome has been implicated in the regulation of GLP-1. We believe that the bacterial metabolite hydrogen sulfide (H2S) can play a protective role in L-cell metabolic stress.

Methods: Our study was conducted on both human NCI H716 and mouse GLUTag GLP-1 secreting L-cells. L-cell stress was assessed using the total reactive oxygen species (ROS) dye DCF-DA. ROS levels were examined during incubation with palmitate (PA), glycated albumin (GA), and the bacterial gas donor GYY4137(H2S). Next, GLP-1 secretion was measured after treating cells with PA and GA, along with H2S using a GLP-1 ELISA.

Results: We have demonstrated that elements of the obese physiological environment: PA and GA, cause an increase of reactive oxygen species (ROS) in L-cells. Specifically, 500μm PA and 200μg/mL GA caused a 75% and 50% increase in ROS generation, respectively. Furthermore, these treatments led to a 25% reduction of GLP-1 secretion in human L-cells. Finally, the microbial gas H₂S reduced basal and PA-induced ROS by nearly half.

Conclusion: The microbial gas H2S reduces metabolic stress in GLP-1 cells. This study will lay the foundation for future work exploring how bacterial products such as prebiotics and probiotics may be used as a treatment for complications associated with obesity and diabetes.


A. Mezouari: None. J. Gagnon: None. R. Nangia: None.


Natural Sciences and Engineering Research Council of Canada (RGPIN-2016-05905)

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