Dataset Information

LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation

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 adipocytes. 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.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bile

SUBMITTER: henrik molina

LAB HEAD: Paul Cohen

PROVIDER: PXD035318 | Pride | 2022-11-21

REPOSITORIES: Pride

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Publications

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

Choi Chan Hee J CHJ Barr William W Zaman Samir S Model Corey C Park Annsea A Koenen Mascha M Lin Zeran Z Szwed Sarah K SK Marchildon Francois F Crane Audrey A Carroll Thomas S TS Molina Henrik H Cohen Paul P

eLife 20221108

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 metabol ...[more]

PMID: 36346018

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Project description:Ramirez2017 - Human global metabolism in brown and white adipocytes Recon 2.1A, an update to Recon 2.1x, is suitable for quantitatively-realistic results for flux balance analysis in human metabolism. This model is described in the article: Integrating Extracellular Flux Measurements and Genome-Scale Modeling Reveals Differences between Brown and White Adipocytes. Ramirez AK, Lynes MD, Shamsi F, Xue R, Tseng YH, Kahn CR, Kasif S, Dreyfuss JM. Cell Rep 2017 Dec; 21(11): 3040-3048 Abstract: White adipocytes are specialized for energy storage, whereas brown adipocytes are specialized for energy expenditure. Explicating this difference can help identify therapeutic targets for obesity. A common tool to assess metabolic differences between such cells is the Seahorse Extracellular Flux (XF) Analyzer, which measures oxygen consumption and media acidification in the presence of different substrates and perturbagens. Here, we integrate the Analyzer's metabolic profile from human white and brown adipocytes with a genome-scale metabolic model to predict flux differences across the metabolic map. Predictions matched experimental data for the metabolite 4-aminobutyrate, the protein ABAT, and the fluxes for glucose, glutamine, and palmitate. We also uncovered a difference in how adipocytes dispose of nitrogenous waste, with brown adipocytes secreting less ammonia and more urea than white adipocytes. Thus, the method and software we developed allow for broader metabolic phenotyping and provide a distinct approach to uncovering metabolic differences. This model is hosted on BioModels Database and identified by: MODEL1703310000. To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation

Publications

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

Similar Datasets

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