LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation
While dysregulation of adipocyte endocrine function plays a central role in obesity and its complications, the vast majority of adipokines remain uncharacterized. We employed bio-orthogonal non-canonical amino acid tagging (BONCAT) and mass spectrometry to comprehensively characterize the secretome...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-11-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/81559 |
| _version_ | 1811220180082098176 |
|---|---|
| author | Chan Hee J Choi William Barr Samir Zaman Corey Model Annsea Park Mascha Koenen Zeran Lin Sarah K Szwed Francois Marchildon Audrey Crane Thomas S Carroll Henrik Molina Paul Cohen |
| author_facet | Chan Hee J Choi William Barr Samir Zaman Corey Model Annsea Park Mascha Koenen Zeran Lin Sarah K Szwed Francois Marchildon Audrey Crane Thomas S Carroll Henrik Molina Paul Cohen |
| author_sort | Chan Hee J Choi |
| collection | DOAJ |
| description | While dysregulation of adipocyte endocrine function plays a central role in obesity and its complications, the vast majority of adipokines remain uncharacterized. We employed bio-orthogonal non-canonical amino acid tagging (BONCAT) and mass spectrometry to comprehensively characterize the secretome of murine visceral and subcutaneous white and interscapular brown adip ocytes. Over 600 proteins were identified, the majority of which showed cell type-specific enrichment. We here describe a metabolic role for leucine-rich α–2 glycoprotein 1 (LRG1) as an obesity-regulated adipokine secreted by mature adipocytes. LRG1 overexpression significantly improved glucose homeostasis in diet-induced and genetically obese mice. This was associated with markedly reduced white adipose tissue macrophage accumulation and systemic inflammation. Mechanistically, we found LRG1 binds cytochrome c in circulation to dampen its pro-inflammatory effect. These data support a new role for LRG1 as an insulin sensitizer with therapeutic potential given its immunomodulatory function at the nexus of obesity, inflammation, and associated pathology. |
| first_indexed | 2024-04-12T07:37:08Z |
| format | Article |
| id | doaj.art-c6f61321c017407b97cd6735f2779d52 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T07:37:08Z |
| publishDate | 2022-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c6f61321c017407b97cd6735f2779d522022-12-22T03:41:54ZengeLife Sciences Publications LtdeLife2050-084X2022-11-011110.7554/eLife.81559LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammationChan Hee J Choi0https://orcid.org/0000-0002-9892-9330William Barr1Samir Zaman2Corey Model3Annsea Park4Mascha Koenen5https://orcid.org/0000-0002-1024-4506Zeran Lin6https://orcid.org/0000-0003-4418-2443Sarah K Szwed7Francois Marchildon8Audrey Crane9Thomas S Carroll10Henrik Molina11https://orcid.org/0000-0001-8950-4990Paul Cohen12https://orcid.org/0000-0002-2786-8585Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, United States; Laboratory of Molecular Metabolism, Rockefeller University, New York, United StatesLaboratory of Molecular Metabolism, Rockefeller University, New York, United StatesLaboratory of Molecular Metabolism, Rockefeller University, New York, United StatesLaboratory of Molecular Metabolism, Rockefeller University, New York, United StatesDepartment of Immunobiology, Yale University, New Haven, United StatesLaboratory of Molecular Metabolism, Rockefeller University, New York, United StatesLaboratory of Molecular Metabolism, Rockefeller University, New York, United StatesWeill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program, New York, United States; Laboratory of Molecular Metabolism, Rockefeller University, New York, United StatesLaboratory of Molecular Metabolism, Rockefeller University, New York, United StatesLaboratory of Molecular Metabolism, Rockefeller University, New York, United StatesBioinformatics Resouce Center, Rockefeller University, New York, United StatesProteomics Resource Center, Rockefeller University, New York, United StatesLaboratory of Molecular Metabolism, Rockefeller University, New York, United StatesWhile dysregulation of adipocyte endocrine function plays a central role in obesity and its complications, the vast majority of adipokines remain uncharacterized. We employed bio-orthogonal non-canonical amino acid tagging (BONCAT) and mass spectrometry to comprehensively characterize the secretome of murine visceral and subcutaneous white and interscapular brown adip ocytes. Over 600 proteins were identified, the majority of which showed cell type-specific enrichment. We here describe a metabolic role for leucine-rich α–2 glycoprotein 1 (LRG1) as an obesity-regulated adipokine secreted by mature adipocytes. LRG1 overexpression significantly improved glucose homeostasis in diet-induced and genetically obese mice. This was associated with markedly reduced white adipose tissue macrophage accumulation and systemic inflammation. Mechanistically, we found LRG1 binds cytochrome c in circulation to dampen its pro-inflammatory effect. These data support a new role for LRG1 as an insulin sensitizer with therapeutic potential given its immunomodulatory function at the nexus of obesity, inflammation, and associated pathology.https://elifesciences.org/articles/81559adipokinesecretomeLRG1cytochrome cobesityinsulin resistance |
| spellingShingle | Chan Hee J Choi William Barr Samir Zaman Corey Model Annsea Park Mascha Koenen Zeran Lin Sarah K Szwed Francois Marchildon Audrey Crane Thomas S Carroll Henrik Molina Paul Cohen LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation eLife adipokine secretome LRG1 cytochrome c obesity insulin resistance |
| title | LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation |
| title_full | LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation |
| title_fullStr | LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation |
| title_full_unstemmed | LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation |
| title_short | LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation |
| title_sort | lrg1 is an adipokine that promotes insulin sensitivity and suppresses inflammation |
| topic | adipokine secretome LRG1 cytochrome c obesity insulin resistance |
| url | https://elifesciences.org/articles/81559 |
| work_keys_str_mv | AT chanheejchoi lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT williambarr lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT samirzaman lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT coreymodel lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT annseapark lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT maschakoenen lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT zeranlin lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT sarahkszwed lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT francoismarchildon lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT audreycrane lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT thomasscarroll lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT henrikmolina lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation AT paulcohen lrg1isanadipokinethatpromotesinsulinsensitivityandsuppressesinflammation |