High-fat diet triggers chemerin-dependent immune reprogramming that exacerbates acute kidney injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1170274 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Obesity presents a known risk factor for acute kidney injury (AKI), but the precise mechanism underlying this phenomenon remains incompletely elucidated. In this study, we demonstrated that short-term high-fat diet (HFD) feeding aggravated kidney injury in AKI mice. Through multi-omics analysis, we identified chemerin (encoded by Rarres2) as a distinctive renal injury-related adipokine enriched in AKI tubular epithelial cells (TECs), particularly following exposure to HFD. Elevated chemerin levels were confirmed in the serum and kidney biopsy samples of AKI patients with obesity, exhibiting a negative correlation with renal function. Rarres2-/- mice were protected from HFD-induced vulnerability toward AKI as well as different types of AKI after standard diet, emphasizing its direct effect on AKI independent of metabolic factors. Mechanism investigation showed the receptor of chemerin-chemerin chemokine-like receptor 1 (CMKLR1) was expressed on renal mononuclear phagocytic cells (MPCs). By single-cell RNA sequencing (scRNA-seq) analysis, unique Cmklr1hi clusters were identified in renal MPCs following AKI, exhibiting enhanced chemotaxis and pro-inflammatory capacity. Functionally, chemerin acted as a chemoattractant to enhance the chemotaxis of Cmklr1hi MPCs. Finally, supplementation of MPCs-derived cytokines reversed kidney injury in Rarres2-/- mice confirming the role of chemerin-CMKLR1 axis in promoting inflammation and kidney damage. Collectively, we identified chemerin as a specific inflammatory and metabolic target that functions through potent pro-inflammatory Cmklr1hi macrophages. Our study suggests that targeting the chemerin-CMKLR1 axis could be a promising therapeutic strategy for AKI patients, especially those with metabolic syndrome.
2025-08-01 | GSE279061 | GEO
Project description:We identified subsets of human CD28- effector CD8 T cells, of CCR7- CD45RO+ effector memory (EM) and CCR7- CD45RO- effector memory RA (EMRA) phenotypes, that express the chemerin receptor CMKLR1 and bind chemerin via the receptor. This study investigates differential gene expression between the chemerin binding and nonbinding human CD8 EMRA T cell subsets.
2024-05-01 | GSE219255 | GEO
Project description:Acute kidney injury (AKI) is a common and life-threatening condition associated with cell death, where ferroptosis plays a critical role. Chemerin, primarily produced in white adipose tissue, has multiple biological functions in renal pathophysiology. However, to date, whether and how chemerin regulates the progression of AKI remain unclear. Here, we found that chemerin expression was reduced in both AKI model mice and cells. Similarly, serum chemerin levels were also decreased in AKI patients. The administration of recombinant chemerin improves renal function in ischemia-reperfusion (I/R) model mice. Chemerin significantly attenuates ferroptosis in kidneys. In TCMK-1 cells, chemerin knockdown further aggravates ferroptosis. Mechanistically, chemerin activates AMP-activated protein kinase (AMPK), which induces the phosphorylation of nuclear factor erythroid 2-related factor 2 (NRF2) in renal tubular cells. Subsequently, NRF2 translocates into the nucleus, where it stimulates the expression of cystine/glutamate antiporter solute carrier (SLC7A11). As a result, cystine uptake and glutathione (GSH) biosynthesis in renal tubular cells were increased, which confers cells with higher capacity against ferroptosis. Overall, our findings indicate that chemerin plays a protective role in AKI by repressing ferroptosis in renal tubular cells, which is likely due to the activation in the AMPK/NRF2/SLC7A11 axis.
2024-12-01 | GSE283126 | GEO
Project description:The goal of this project is to investigate the mechanisms through which high fat diet (HFD) exacerbates colitis via the liver-gut axis, particularly focusing on liver dysregulated lipid metabolism and intestinal autophagy. We examined liver transcriptomes of C57BL6/J mice fed a control diet (CD) or HFD with or without dextran sulfate sodium (DSS) by RNA seq analysis.
2025-04-04 | GSE293183 | GEO
Project description:The goal of this project is to investigate the mechanisms through which high fat diet (HFD) exacerbates colitis via the liver-gut axis, particularly focusing on liver dysregulated lipid metabolism and intestinal autophagy. We examined colon transcriptomes of C57BL6/J mice fed a control diet (CD) or HFD with or without dextran sulfate sodium (DSS) by RNA seq analysis.
2025-07-02 | GSE293222 | GEO
Project description:Chemerin is a leukocyte chemoattractant and an adipokine. Overexpression of chemerin by tumor cells or the host inhibits tumor progression in different mouse models, through a mechanism involving the chemerin receptor CMKLR1 and impairment of endothelial cell/pericyte interactions in neovessels.
2019-05-05 | GSE98672 | GEO
Project description:The most common subset of renal carcinoma, clear cell renal cell carcinoma (ccRCC), is characterized by accentuated accumulation of neutral lipids in lipid droplets and adipogenic trans-differentiation. Because obesity is a major risk factor in the development of ccRCC, we investigated the role of the adipokines in driving lipid metabolism and tumorigenesis in ccRCC. Through in silico screening, we identified the adipokine chemerin as candidate pro-oncogenic factor that is overexpressed in tumors and prognostic for patient outcome. Both ccRCC patient tumor tissues and serum exhibit elevated chemerin levels as compared to normal controls in an obesity-dependent manner. Attenuation of chemerin by several approaches in ccRCC cells led to significant impairments of tumor growth in both in vitro and in vivo models. A multi-omic approach revealed that chemerin suppresses fatty acid oxidation and maintains fatty acid levels which feed into transcriptional activation of hypoxia-inducible factor 2 (HIF2) expression. Suppression of chemerin therefore induced excess fatty acid oxidation and led to ferroptosis. CoQ and mitochondrial complex IV, derived mainly from lipid, were affected after chemerin inhibition, contributing to mitochondrial dysfunction and lipid reactive oxygen species production. Monoclonal antibody targeting chemerin led to reduced lipid storage, increased cell death, and diminished tumor growth, strengthening the translational potential of chemerin inhibition. Collectively, the results suggest that obesity and tumor cells contribute to ccRCC through the expression of chemerin, which is indispensable in ccRCC biology.
2021-08-11 | GSE159716 | GEO
Project description:Chemerin triggers migration of a CD8 T cell subset with natural killer cell functions
| PRJNA907810 | ENA
Project description:Osteopontin Exacerbates High-Fat Diet-induced Metabolic Disorders in a microbiome-dependent Manner
| PRJNA893378 | ENA
Project description:High-Fat Diet-Induced Liver-Gut Crosstalk Suppresses Autophagy and Exacerbates Colitis [colon]
| PRJNA1243378 | ENA