Abstract
Circulating palmitic acid (PA) is increased in obesity and causes metabolic stress, leading to diabetes. This includes the impairment of the glucoregulatory hormone glucagon-like peptide-1 (GLP-1) secreted from intestinal L-cells. Recently, the anti-inflammatory gasotransmitter hydrogen sulfide (H2S) has been implicated in the enhancement of GLP-1 secretion. We hypothesized that H2S can reduce the oxidative stress caused by palmitate and play a protective role in L-cell function. This study was conducted on both human and mouse L-cells and a mouse model of Western diet (WD)-induced obesity. PA-induced L-cell stress was assessed using DCF-DA. H2S was delivered using the donor GYY4137. C57BL/6 mice were fed either chow diet or PA-enriched WD for 20 weeks with ongoing measurements of glycemia and GLP-1 secretion. In both L-cell models, we demonstrated that PA caused an increase in reactive oxygen species (ROS). This ROS induction was partially blocked by the H2S administration. In mice, the WD elevated body weight in both sexes and elevated fasting blood glucose and lipid peroxidation in males. Additionally, a single GYY4137 injection improved oral glucose tolerance in WD-fed male mice and also enhanced glucose-stimulated GLP-1 release. To conclude, H2S reduces oxidative stress in GLP-1 cells and can improve glucose clearance in mice.
Highlights
Obesity has reached epidemic proportions worldwide with a prevalence that has tripled since 2016, and a projection that nearly half of the US population will be obese by 2030, as reported by the World Health Organization
Glucagon-like peptide-1 (GLP-1) secretion may be impaired in obese individuals, and this may contribute to the hyperglycemia and decreased satiety seen during obesity [9]
We developed a protocol for reactive oxygen species (ROS) detection and examined the effect of palmitic acid (PA) on ROS production in NCI-H716 and GLUTag cell lines
Summary
Obesity has reached epidemic proportions worldwide with a prevalence that has tripled since 2016, and a projection that nearly half of the US population will be obese by 2030, as reported by the World Health Organization. One group of anti-obesity treatments that are being used are the Glucagon-like peptide-1 (GLP-1) drugs [3]. These either prolong the half-life of endogenous GLP-1 such as dipeptidyl peptidase-4 (DPP4) inhibitors, or act as GLP-1 receptor agonists. The latter successfully target obesity (1–3 kg after 26/30 weeks), whereas Dipeptidyl peptidase-4 inhibitors are weight—neutral [4,5]. GLP-1 secretion may be impaired in obese individuals, and this may contribute to the hyperglycemia and decreased satiety seen during obesity [9]. The mechanism leading to obesity-induced GLP-1 impairment is not clearly known
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call