Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis
Abstract Background Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death. Methods We performed lipidomics using thr...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | Cell Communication and Signaling |
| Online Access: | https://doi.org/10.1186/s12964-023-01437-1 |
| _version_ | 1797273815732977664 |
|---|---|
| author | Soumyadeep Sarkar Cailin Deiter Jennifer E. Kyle Michelle A. Guney Dylan Sarbaugh Ruichuan Yin Xiangtang Li Yi Cui Mireia Ramos-Rodriguez Carrie D. Nicora Farooq Syed Jonas Juan-Mateu Charanya Muralidharan Lorenzo Pasquali Carmella Evans-Molina Decio L. Eizirik Bobbie-Jo M. Webb-Robertson Kristin Burnum-Johnson Galya Orr Julia Laskin Thomas O. Metz Raghavendra G. Mirmira Lori Sussel Charles Ansong Ernesto S. Nakayasu |
| author_facet | Soumyadeep Sarkar Cailin Deiter Jennifer E. Kyle Michelle A. Guney Dylan Sarbaugh Ruichuan Yin Xiangtang Li Yi Cui Mireia Ramos-Rodriguez Carrie D. Nicora Farooq Syed Jonas Juan-Mateu Charanya Muralidharan Lorenzo Pasquali Carmella Evans-Molina Decio L. Eizirik Bobbie-Jo M. Webb-Robertson Kristin Burnum-Johnson Galya Orr Julia Laskin Thomas O. Metz Raghavendra G. Mirmira Lori Sussel Charles Ansong Ernesto S. Nakayasu |
| author_sort | Soumyadeep Sarkar |
| collection | DOAJ |
| description | Abstract Background Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death. Methods We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling. Results Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholines with polyunsaturated fatty acids and their hydrolyzing enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of ADP-ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-mediated reduction of the histone methylation polycomb complex PRC2 component Suz12, upregulating the expression of Arh3, which in turn decreases cell apoptosis. Conclusions Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids. Video Abstract |
| first_indexed | 2024-03-07T14:49:38Z |
| format | Article |
| id | doaj.art-6b57b4f4064a4390ae8f0840effa40ac |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-07T14:49:38Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-6b57b4f4064a4390ae8f0840effa40ac2024-03-05T19:47:15ZengBMCCell Communication and Signaling1478-811X2024-02-0122111710.1186/s12964-023-01437-1Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitisSoumyadeep Sarkar0Cailin Deiter1Jennifer E. Kyle2Michelle A. Guney3Dylan Sarbaugh4Ruichuan Yin5Xiangtang Li6Yi Cui7Mireia Ramos-Rodriguez8Carrie D. Nicora9Farooq Syed10Jonas Juan-Mateu11Charanya Muralidharan12Lorenzo Pasquali13Carmella Evans-Molina14Decio L. Eizirik15Bobbie-Jo M. Webb-Robertson16Kristin Burnum-Johnson17Galya Orr18Julia Laskin19Thomas O. Metz20Raghavendra G. Mirmira21Lori Sussel22Charles Ansong23Ernesto S. Nakayasu24Biological Sciences Division, Pacific Northwest National LaboratoryBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical CenterBiological Sciences Division, Pacific Northwest National LaboratoryBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical CenterBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical CenterDepartment of Chemistry, Purdue UniversityDepartment of Chemistry, Purdue UniversityEnvironmental and Molecular Sciences Laboratory, Pacific Northwest National LaboratoryEndocrine Regulatory Genomics, Department of Experimental & Health Sciences, University Pompeu FabraBiological Sciences Division, Pacific Northwest National LaboratoryCenter for Diabetes and Metabolic Diseases and the Herman B Wells Center for Pediatric Research, Indiana University School of MedicineULB Center for Diabetes Research, Université Libre de Bruxelles (ULB)Kovler Diabetes Center and Department of Medicine, The University of ChicagoEndocrine Regulatory Genomics, Department of Experimental & Health Sciences, University Pompeu FabraCenter for Diabetes and Metabolic Diseases and the Herman B Wells Center for Pediatric Research, Indiana University School of MedicineULB Center for Diabetes Research, Université Libre de Bruxelles (ULB)Biological Sciences Division, Pacific Northwest National LaboratoryEnvironmental and Molecular Sciences Laboratory, Pacific Northwest National LaboratoryEnvironmental and Molecular Sciences Laboratory, Pacific Northwest National LaboratoryDepartment of Chemistry, Purdue UniversityBiological Sciences Division, Pacific Northwest National LaboratoryKovler Diabetes Center and Department of Medicine, The University of ChicagoBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical CenterBiological Sciences Division, Pacific Northwest National LaboratoryBiological Sciences Division, Pacific Northwest National LaboratoryAbstract Background Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death. Methods We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling. Results Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholines with polyunsaturated fatty acids and their hydrolyzing enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of ADP-ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-mediated reduction of the histone methylation polycomb complex PRC2 component Suz12, upregulating the expression of Arh3, which in turn decreases cell apoptosis. Conclusions Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids. Video Abstracthttps://doi.org/10.1186/s12964-023-01437-1 |
| spellingShingle | Soumyadeep Sarkar Cailin Deiter Jennifer E. Kyle Michelle A. Guney Dylan Sarbaugh Ruichuan Yin Xiangtang Li Yi Cui Mireia Ramos-Rodriguez Carrie D. Nicora Farooq Syed Jonas Juan-Mateu Charanya Muralidharan Lorenzo Pasquali Carmella Evans-Molina Decio L. Eizirik Bobbie-Jo M. Webb-Robertson Kristin Burnum-Johnson Galya Orr Julia Laskin Thomas O. Metz Raghavendra G. Mirmira Lori Sussel Charles Ansong Ernesto S. Nakayasu Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis Cell Communication and Signaling |
| title | Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis |
| title_full | Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis |
| title_fullStr | Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis |
| title_full_unstemmed | Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis |
| title_short | Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis |
| title_sort | regulation of β cell death by adp ribosylhydrolase arh3 via lipid signaling in insulitis |
| url | https://doi.org/10.1186/s12964-023-01437-1 |
| work_keys_str_mv | AT soumyadeepsarkar regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT cailindeiter regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT jenniferekyle regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT michelleaguney regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT dylansarbaugh regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT ruichuanyin regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT xiangtangli regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT yicui regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT mireiaramosrodriguez regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT carriednicora regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT farooqsyed regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT jonasjuanmateu regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT charanyamuralidharan regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT lorenzopasquali regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT carmellaevansmolina regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT decioleizirik regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT bobbiejomwebbrobertson regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT kristinburnumjohnson regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT galyaorr regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT julialaskin regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT thomasometz regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT raghavendragmirmira regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT lorisussel regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT charlesansong regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis AT ernestosnakayasu regulationofbcelldeathbyadpribosylhydrolasearh3vialipidsignalingininsulitis |