GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation
Hydrogen sulfide (H2S) 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 m...
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Frontiers Media S.A.
2018-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00966/full |
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| author | Jun Zhou Xiao-Hui Lv Jun-Juan Fan Li-Yun Dang Kun Dong Bo Gao Ao-Qi Song Wen-Ning Wu |
| author_facet | Jun Zhou Xiao-Hui Lv Jun-Juan Fan Li-Yun Dang Kun Dong Bo Gao Ao-Qi Song Wen-Ning Wu |
| author_sort | Jun Zhou |
| collection | DOAJ |
| description | Hydrogen sulfide (H2S) 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 H2S via CaMKKβ/AMPK pathway. But the role of H2S in ARC and appetite has not been reported. Here we studied the orexigenic effect of H2S and the mechanisms by means of GYY4137, a water soluble and slow-releasing donor of H2S, and protein sulfur-sulfhydrylation analysis. We demonstrated that GYY4137-derived H2S 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 H2S enhances appetite through protein sulfur-sulfhydrylation and the activation of AMPK and NPY function in ARC. |
| first_indexed | 2024-12-23T20:04:51Z |
| format | Article |
| id | doaj.art-f7b41882abf242e0bcf15e49d359ce2c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T20:04:51Z |
| publishDate | 2018-08-01 |
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| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f7b41882abf242e0bcf15e49d359ce2c2022-12-21T17:32:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-08-01910.3389/fphar.2018.00966395024GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK ActivationJun Zhou0Xiao-Hui Lv1Jun-Juan Fan2Li-Yun Dang3Kun Dong4Bo Gao5Ao-Qi Song6Wen-Ning Wu7Department of Pharmacy, Xi’an Chest Hospital, Shaanxi University of Chinese Medicine, Xi’an, ChinaDepartment of Pharmacy, Xi’an Chest Hospital, Shaanxi University of Chinese Medicine, Xi’an, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Anhui Medical University, Hefei, ChinaDepartment of Pharmacy, Xi’an Chest Hospital, Shaanxi University of Chinese Medicine, Xi’an, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Anhui Medical University, Hefei, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Anhui Medical University, Hefei, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Anhui Medical University, Hefei, ChinaDepartment of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Anhui Medical University, Hefei, ChinaHydrogen sulfide (H2S) 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 H2S via CaMKKβ/AMPK pathway. But the role of H2S in ARC and appetite has not been reported. Here we studied the orexigenic effect of H2S and the mechanisms by means of GYY4137, a water soluble and slow-releasing donor of H2S, and protein sulfur-sulfhydrylation analysis. We demonstrated that GYY4137-derived H2S 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 H2S enhances appetite through protein sulfur-sulfhydrylation and the activation of AMPK and NPY function in ARC.https://www.frontiersin.org/article/10.3389/fphar.2018.00966/fullhydrogen sulfidearcuate nucleusGYY4137food intakeAMPKsulfur-sulfhydrylation |
| spellingShingle | Jun Zhou Xiao-Hui Lv Jun-Juan Fan Li-Yun Dang Kun Dong Bo Gao Ao-Qi Song Wen-Ning Wu GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation Frontiers in Pharmacology hydrogen sulfide arcuate nucleus GYY4137 food intake AMPK sulfur-sulfhydrylation |
| title | GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation |
| title_full | GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation |
| title_fullStr | GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation |
| title_full_unstemmed | GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation |
| title_short | GYY4137 Promotes Mice Feeding Behavior via Arcuate Nucleus Sulfur-Sulfhydrylation and AMPK Activation |
| title_sort | gyy4137 promotes mice feeding behavior via arcuate nucleus sulfur sulfhydrylation and ampk activation |
| topic | hydrogen sulfide arcuate nucleus GYY4137 food intake AMPK sulfur-sulfhydrylation |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00966/full |
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