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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE185484 | GEO | 2022/03/04

REPOSITORIES: GEO

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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

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

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. 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

2022-03-04 | GSE185481 | GEO

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

2022-03-04 | GSE185483 | GEO

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

2022-03-04 | GSE185482 | GEO

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.

| PRJNA769145 | ENA

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]

| PRJNA769184 | ENA

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]

| PRJNA769182 | ENA

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]

| PRJNA769183 | ENA

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 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.

| S-EPMC9674348 | biostudies-literature

The obesity-induced adipokine sST2 exacerbates adipose Treg and ILC2 depletion and promotes insulin resistance.

Project description:Depletion of fat-resident regulatory T cells (Tregs) and group 2 innate lymphoid cells (ILC2s) has been causally linked to obesity-associated insulin resistance. However, the molecular nature of the pathogenic signals suppress adipose Tregs and ILC2s in obesity remains unknown. Here, we identified the soluble isoform of interleukin (IL)-33 receptor ST2 (sST2) as an obesity-induced adipokine that attenuates IL-33 signaling and disrupts Treg/ILC2 homeostasis in adipose tissue, thereby exacerbates obesity-associated insulin resistance in mice. We demonstrated sST2 is a target of TNF? signaling in adipocytes that is countered by Zbtb7b. Fat-specific ablation of Zbtb7b augments adipose sST2 gene expression, leading to diminished fat-resident Tregs/ILC2s, more pronounced adipose tissue inflammation and fibrosis, and impaired glucose homeostasis in mice. Mechanistically, Zbtb7b suppresses NF-?B activation in response to TNF? through destabilizing I?B?. These findings uncover an adipokine-immune signaling pathway that is engaged in obesity to drive the pathological changes of the immunometabolic landscape.

| S-EPMC7220368 | biostudies-literature

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