Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes
Objective: Exposure of adipocytes to ‘cool’ temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-05-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877824000474 |
| _version_ | 1797246831519858688 |
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| author | Hiroyuki Mori Sydney K. Peterson Rachel C. Simmermon Katherine A. Overmyer Akira Nishii Emma Paulsson Ziru Li Annie Jen Romina M. Uranga Jessica N. Maung Warren T. Yacawych Kenneth T. Lewis Rebecca L. Schill Taryn Hetrick Ryo Seino Ken Inoki Joshua J. Coon Ormond A. MacDougald |
| author_facet | Hiroyuki Mori Sydney K. Peterson Rachel C. Simmermon Katherine A. Overmyer Akira Nishii Emma Paulsson Ziru Li Annie Jen Romina M. Uranga Jessica N. Maung Warren T. Yacawych Kenneth T. Lewis Rebecca L. Schill Taryn Hetrick Ryo Seino Ken Inoki Joshua J. Coon Ormond A. MacDougald |
| author_sort | Hiroyuki Mori |
| collection | DOAJ |
| description | Objective: Exposure of adipocytes to ‘cool’ temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in adipocytes. Method: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme's function in adipocyte physiology. Results: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes. Conclusion: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes. |
| first_indexed | 2024-04-24T19:49:03Z |
| format | Article |
| id | doaj.art-f76e22ea51ec4cc08977dd19997e3c5d |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-24T19:49:03Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-f76e22ea51ec4cc08977dd19997e3c5d2024-03-25T04:17:31ZengElsevierMolecular Metabolism2212-87782024-05-0183101916Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytesHiroyuki Mori0Sydney K. Peterson1Rachel C. Simmermon2Katherine A. Overmyer3Akira Nishii4Emma Paulsson5Ziru Li6Annie Jen7Romina M. Uranga8Jessica N. Maung9Warren T. Yacawych10Kenneth T. Lewis11Rebecca L. Schill12Taryn Hetrick13Ryo Seino14Ken Inoki15Joshua J. Coon16Ormond A. MacDougald17Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA; Corresponding author.Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USAMorgridge Institute for Research, Madison, WI, USA; National Center for Quantitative Biology of Complex Systems, Madison, WI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA; Department of Chemistry, University of Wisconsin, Madison, WI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USADojindo Molecular Technologies, Inc., Rockville, MD, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USAMorgridge Institute for Research, Madison, WI, USA; National Center for Quantitative Biology of Complex Systems, Madison, WI, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI, USA; Department of Chemistry, University of Wisconsin, Madison, WI, USADepartment of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Corresponding author. Department of Molecular & Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA.Objective: Exposure of adipocytes to ‘cool’ temperatures often found in the periphery of the body induces expression of Stearoyl-CoA Desaturase-1 (Scd1), an enzyme that converts saturated fatty acids to monounsaturated fatty acids. The goal of this study is to further investigate the roles of Scd in adipocytes. Method: In this study, we employed Scd1 knockout cells and mouse models, along with pharmacological Scd1 inhibition to dissect the enzyme's function in adipocyte physiology. Results: Our study reveals that production of monounsaturated lipids by Scd1 is necessary for fusion of autophagosomes to lysosomes and that with a Scd1-deficiency, autophagosomes accumulate. In addition, Scd1-deficiency impairs lysosomal and autolysosomal acidification resulting in vacuole accumulation and eventual cell death. Blocking autophagosome formation or supplementation with monounsaturated fatty acids maintains vitality of Scd1-deficient adipocytes. Conclusion: This study demonstrates the indispensable role of Scd1 in adipocyte survival, with its inhibition in vivo triggering autophagy-dependent cell death and its depletion in vivo leading to the loss of bone marrow adipocytes.http://www.sciencedirect.com/science/article/pii/S2212877824000474Scd1Stearoyl CoA Desaturase 1ADCDAutophagy-dependent cell deathBMATBone marrow adipose tissue |
| spellingShingle | Hiroyuki Mori Sydney K. Peterson Rachel C. Simmermon Katherine A. Overmyer Akira Nishii Emma Paulsson Ziru Li Annie Jen Romina M. Uranga Jessica N. Maung Warren T. Yacawych Kenneth T. Lewis Rebecca L. Schill Taryn Hetrick Ryo Seino Ken Inoki Joshua J. Coon Ormond A. MacDougald Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes Molecular Metabolism Scd1 Stearoyl CoA Desaturase 1 ADCD Autophagy-dependent cell death BMAT Bone marrow adipose tissue |
| title | Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes |
| title_full | Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes |
| title_fullStr | Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes |
| title_full_unstemmed | Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes |
| title_short | Scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes |
| title_sort | scd1 and monounsaturated lipids are required for autophagy and survival of adipocytes |
| topic | Scd1 Stearoyl CoA Desaturase 1 ADCD Autophagy-dependent cell death BMAT Bone marrow adipose tissue |
| url | http://www.sciencedirect.com/science/article/pii/S2212877824000474 |
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