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

Publication Type	Academic Article
Authors	Choi C, Barr W, Zaman S, Model C, Park A, Koenen M, Lin Z, Szwed S, Marchildon F, Crane A, Carroll T, Molina H, Cohen P
Journal	Elife
Volume	11
Date Published	11/08/2022
ISSN	2050-084X
Keywords	Adipokines, Insulin Resistance
Abstract	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.
DOI	10.7554/eLife.81559
PubMed ID	36346018
PubMed Central ID	PMC9674348