The molecular interactions that regulate chronic inflammation underlying metabolic disease remain largely unknown. Since the CD24-Siglec interaction regulates inflammatory response to danger-associated molecular patterns (DAMPs), we have generated multiple mouse strains with single or combined mutations of Cd24 or Siglec genes to explore the role of the CD24-Siglec interaction in metaflammation and metabolic disorder. Here, we report that the CD24-Siglec-E axis, but not other Siglecs, is a key suppressor of obesity-related metabolic dysfunction. Inactivation of the CD24-Siglec-E pathway exacerbates, while CD24Fc treatment alleviates, diet-induced metabolic disorders, including obesity, dyslipidemia, insulin resistance, and nonalcoholic steatohepatitis (NASH). Mechanistically, sialylation-dependent recognition of CD24 by Siglec-E induces SHP-1 recruitment and represses metaflammation to protect against metabolic syndrome. A first-in-human study of CD24Fc (NCT02650895) supports the significance of this pathway in human lipid metabolism and inflammation. These findings identify the CD24-Siglec-E axis as an innate immune checkpoint against metaflammation and metabolic disorder and suggest a promising therapeutic target for metabolic disease.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9393047 | PMC |
| http://dx.doi.org/10.1016/j.cmet.2022.07.005 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular pathological characteristics and mechanisms of the liver in metabolic disease-susceptible transgenic pigs.
Life Sci
February 2025
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China. Electronic address:
Aims: This study aimed to explore the molecular pathological mechanisms of the liver in metabolic disease-susceptible transgenic pigs via multiomics analysis.
Materials And Methods: The triple-transgenic (PNPLA3-GIPR-hIAPP) pig model (TG pig) was successfully constructed in our laboratory via the CRISPR/Cas9 technique previously described. Wild-type (WT) pigs and TG pigs after 2 or 12 months of high-fat and high-sucrose diet (HFHSD) induction (WT2, TG2, WT12, and TG12 groups, respectively) were used as materials.
Adipose tissue dysfunction leads to abnormal lipid metabolism and high inflammation levels. This research aims to explore the role of Serpina3c, which is highly expressed in adipocytes, in obesity-related hypertriglyceridemia and metaflammation. Serpina3c global knockout (KO) mice, adipocyte-specific Serpina3c overexpressing mice, Serpina3c knockdown (KD) mice, and hypoxia-inducible factor 1 alpha (Hif1α) KD mice were fed a high-fat diet (HFD) for 16 weeks to generate obesity-related hypertriglyceridemia mice models.
View Article and Find Full Text PDFPlasma soluble TIM-3 is increased in normoglycemic South Asian women compared to Nordic women after gestational diabetes mellitus and associated with markers of metaflammation.
Heliyon
November 2024
Research Institute for Internal Medicine, Oslo University Hospital, Oslo, Norway.
Article Synopsis
- South Asian women have a heightened risk of developing type 2 diabetes mellitus (T2DM) after experiencing gestational diabetes mellitus (GDM) compared to white Nordic women, potentially linked to low-grade immune activation.
- A study compared plasma levels of certain immune markers (sTIM-3, sCD25, sCD27, sLAG-3) in 266 women with a history of GDM and found higher sTIM-3 levels in South Asian women, especially those with normal glucose tolerance.
- The research indicated that differences in adipose insulin resistance between the ethnic groups might be partially explained by sTIM-3 levels and waist-height ratio, emphasizing the role of immune cell activation in metabolic issues among South Asian
A Cross-Sectional Study: Systematic Quantification of Chemerin in Human Cerebrospinal Fluid.
Biomedicines
November 2024
Department of Neurology, University of Giessen, Klinikstr. 33, 35392 Giessen, Germany.
Background: Dysregulation of adipokines is considered a key mechanism of chronic inflammation in metabolic syndrome. Some adipokines affect food intake by crossing the blood/brain barrier. The adipokine chemerin is associated with metabolic syndrome, cardiovascular diseases and immune response.
View Article and Find Full Text PDFEstrogen: the forgotten player in metaflammation.
Front Pharmacol
November 2024
West China School of Pharmacy, West China School of Basic Medical Sciences and Forensic Medicine, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Metaflammation is low-grade inflammation triggered by chronic metabolic imbalance and caused by dysregulated metabolites in metabolic inflammatory syndrome (MIS), which includes four diseases: obesity, type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and nonalcoholic fatty liver diseases (NAFLD, recently proposed to be replaced by metabolic dysfunction-associated steatotic liver disease, MASLD). These diseases exhibit apparent sex dimorphism as regards MIS. Estrogen not only plays a crucial role in gender differences in adults but also possesses an anti-inflammatory effect on many metabolic diseases.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!