AUTHOR=Zhou Jun , Lv Xiao-Hui , Fan Jun-Juan , Dang Li-Yun , Dong Kun , Gao Bo , Song Ao-Qi , Wu Wen-Ning 

TITLE=GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00966

DOI=10.3389/fphar.2018.00966

ISSN=1663-9812

ABSTRACT=<p>Hydrogen sulfide (H<sub>2</sub>S) is an endogenous gaseous molecule and plays important biological and neurochemical roles in many processes such as the neural activity and immunity. The arcuate nucleus (ARC) of hypothalamus is a control center for appetite and energy metabolism. AMPK is a gage kinase in the monitoring of energy status and regulation of energy metabolism, and it can be activated by H<sub>2</sub>S via CaMKKβ/AMPK pathway. But the role of H<sub>2</sub>S in ARC and appetite has not been reported. Here we studied the orexigenic effect of H<sub>2</sub>S and the mechanisms by means of GYY4137, a water soluble and slow-releasing donor of H<sub>2</sub>S, and protein sulfur-sulfhydrylation analysis. We demonstrated that GYY4137-derived H<sub>2</sub>S increased food intake of mice, augmented the production of neuropeptide Y (NPY), and elevated the protein sulfur-sulfhydrylation level and the activation of AMPK and CaMKKβ in ARC. Blocking sulfur-sulfhydrylation with DTT eliminated GYY4137-induced activation of AMPK and CaMKKβ. DTT and preventing AMPK activation in ARC with Compound C and Ara-A could both attenuate the orexigenic effect of GYY4137. These findings suggest that H<sub>2</sub>S enhances appetite through protein sulfur-sulfhydrylation and the activation of AMPK and NPY function in ARC.</p>