Sulfhydration of perilipin 1 is involved in the inhibitory effects of cystathionine gamma lyase/hydrogen sulfide on adipocyte lipolysis |
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| Affiliation: | 1. Laboratory Animal Center, Xi’an Jiaotong University Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China;2. The Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710077, China;3. Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an, Shaanxi 710021, China;4. Shannxi Pharmaceutical Development Center, Shannxi Pharmaceutical Holding Group Co., LTD, Xi’an, Shaanxi 710075, China;5. Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan;1. Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Greece;2. Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece;3. Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA;1. Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, China;2. Center for Cancer Research, Medical school, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China;3. Department of Pathology, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan;4. Department of Genetics and Molecular Biology, Medical College of Xi’an Jiaotong University, Xi’an, Shaanxi, China;1. Department of Pathophysiology, Medical University, Lublin, Poland;2. Department of Neurology, Medical University, Lublin, Poland |
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| Abstract: | Hydrogen sulfide (H2S) is a novel adipokine mediating glucose uptake, lipid storage and mobilization, thus contributing to the genesis of obesity and associated diseases. Our previous work demonstrated that H2S inhibited isoproterenol-stimulated lipolysis by reducing the phosphorylation of perilipin 1 (plin-1), a lipid-droplet protein blocking lipase access. How H2S modulates plin-1 phosphorylation is still unclear. Our present study found that an H2S donor slightly increased adipose tissue weight and reduced lipolysis in mice; by contrast, deleting the key H2S generation enzyme cystathionine gamma lyase (CSE) in adipocytes lowered adipose accumulation and enhanced lipolysis. Intriguingly, an H2S donor induced sulfhydration of plin-1 but not hormone-sensitive lipase, and CSE deletion abolished the post-translational modification of plin-1. During isoproterenol-stimulated lipolysis, plin-1 sulfhydration was associated with reduced phosphorylation, and removing sulfhydration by dithiothreitol recovered the phosphorylation. Finally, plin-1 knockout abolished the effect of H2S on lipolysis, which indicates that plin-1 sulfhydration is a major direct target of H2S in lipolysis. We have identified a new post-translation modification, sulfhydration (direct action by H2S) of plin-1, causing reduced phosphorylation then decreased lipolysis. This finding also highlights a novel molecular regulatory mechanism of lipolysis. |
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| Keywords: | Cystathionine gamma lyase Hydrogen sulfide Sulfhydration Perilipin Lipolysis Adipocyte |
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