LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation.
LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation.
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DOI：
10.7554/elife.81559
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发表时间：
2022-11-08
期刊：
影响因子：
7.7
通讯作者：
Cohen P
中科院分区：
文献类型：
--
作者：
Choi CHJ;Barr W;Zaman S;Model C;Park A;Koenen M;Lin Z;Szwed SK;Marchildon F;Crane A;Carroll TS;Molina H;Cohen P
虽然脂肪细胞内分泌功能失调在肥胖及其并发症中起着重要作用，但绝大多数脂肪因子仍不清楚。我们采用生物正交非规范氨基酸标记（BONCAT）和质谱法，全面表征小鼠内脏和皮下白色和肩胛间棕色脂肪细胞的分泌组。鉴定了600多种蛋白质，其中大多数显示出细胞类型特异性富集。我们在这里描述了富含亮氨酸的α-2糖蛋白1（LRG 1）作为成熟脂肪细胞分泌的肥胖调节脂肪因子的代谢作用。LRG 1过表达显著改善饮食诱导和遗传性肥胖小鼠的葡萄糖稳态。这与白色脂肪组织巨噬细胞蓄积和全身炎症显著减少相关。从机制上讲，我们发现LRG 1结合循环中的细胞色素c以抑制其促炎作用。这些数据支持LRG 1作为胰岛素增敏剂的新作用，鉴于其在肥胖、炎症和相关病理学关系中的免疫调节功能，其具有治疗潜力。
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.