Skip to Content
Merck
  • LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation.

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

eLife (2022-11-09)
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
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.

MATERIALS
Product Number
Brand
Product Description

Millipore
Anti-FLAG® M2 Magnetic Beads, affinity isolated antibody
Sigma-Aldrich
Cytochrome c from equine heart, ≥95% (SDS-PAGE)
Sigma-Aldrich
Anti-LRG1 antibody produced in rabbit, Ab1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution