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LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [array]

ABSTRACT: Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. In this study, microarray was used to identify genes that are differentially expressed during adipocyte differentiation, further screening based on microarray result identified Leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine. Expression data of pre-adipocytes and mature adipocytes

ORGANISM(S): Mus musculus

PROVIDER: GSE185481 | GEO | 2022/03/04

REPOSITORIES: GEO

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LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [liver_RNA-seq]

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LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [heaptocyte_RNA-seq]

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LRG1 is an adipokine that promotes insulin sensitivity and suppresses inflammation

Project description: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.

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LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance.

Project description:LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance.

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LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [array]

Project description:LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [array]

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LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [liver_RNA-seq]

Project description:LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [liver_RNA-seq]

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LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [heaptocyte_RNA-seq]

Project description:LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance [heaptocyte_RNA-seq]

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Single-Cell RNA Sequencing Unveils Lrg1's Role in Cerebral Ischemia‒Reperfusion Injury by Modulating Various Cells

Project description:Leucine-rich alpha-2 glycoprotein 1 (Lrg1) appears to be associated with the progression of cerebral ischemia-reperfusion injury, but its exact mechanism remains unknown. Here, we utilized scRNA-seq to compare the microenvironmental changes in the brains of Lrg1 knockout mice and wild-type mice following MCAO/R, in order to elucidate the role of Lrg1 after MCAO/R.

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RNA sequencing of keratinocytes with or without LRG1 addition

Project description:Leucine-rich-alpha-2-glycoprotein1 (LRG1), a highly conserved member of the leucine-rich repeat family of proteins, has been reported to be involved in several tumors. Previous studies showed that it has great importance in epithelial–mesenchymal transition in colorectal cancer and could promote glioma cell lines invasion and migration. Despite the intimate relationships between LRG1 and migration in cancer research, its role in wound repair or re-epithelialization has not been uncovered. So we dicided using keratinocytes to see its transcriptomes changing after LRG1 addition.

2019-11-11 | GSE122527 | GEO

LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance.

Project description:Dysregulation in adipokine biosynthesis and function contributes to obesity-induced metabolic diseases. However, the identities and functions of many of the obesity-induced secretory molecules remain unknown. Here, we report the identification of leucine-rich alpha-2-glycoprotein 1 (LRG1) as an obesity-associated adipokine that exacerbates high fat diet-induced hepatosteatosis and insulin resistance. Serum levels of LRG1 were markedly elevated in obese humans and mice compared with their respective controls. LRG1 deficiency in mice greatly alleviated diet-induced hepatosteatosis, obesity, and insulin resistance. Mechanistically, LRG1 bound with high selectivity to the liver and promoted hepatosteatosis by increasing de novo lipogenesis and suppressing fatty acid β-oxidation. LRG1 also inhibited hepatic insulin signaling by downregulating insulin receptor substrates 1 and 2. Our study identified LRG1 as a key molecule that mediates the crosstalk between adipocytes and hepatocytes in diet-induced hepatosteatosis and insulin resistance. Suppressing LRG1 expression and function may be a promising strategy for the treatment of obesity-related metabolic diseases.

| S-EPMC8670837 | biostudies-literature

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