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Publication : LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation.

First Author  Choi CHJ Year  2022
Journal  Elife Volume  11
PubMed ID  36346018 Mgi Jnum  J:337151
Mgi Id  MGI:7386460 Doi  10.7554/eLife.81559
Citation  Choi CHJ, et al. (2022) LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation. Elife 11
abstractText  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 alpha-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.
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