Soluble CLEC2 Extracellular Domain Improves Glucose and Lipid Homeostasis by Regulating Liver Kupffer Cell Polarization.
EBioMedicine
; 2(3): 214-24, 2015 Mar.
Article
en En
| MEDLINE
| ID: mdl-26151067
ABSTRACT
The polarization of tissue resident macrophages toward the alternatively activated, anti-inflammatory M2 phenotype is believed to positively impact obesity and insulin resistance. Here we show that the soluble form of the extracellular domain (ECD) of C-type lectin-like receptor 2, CLEC2, regulates Kupffer cell polarization in the liver and improves glucose and lipid parameters in diabetic animal models. Over-expression of Fc-CLEC2(ECD) in mice via in vivo gene delivery, or injection of recombinant Fc-CLEC2(ECD) protein, results in a reduction of blood glucose and liver triglyceride levels and improves glucose tolerance. Furthermore, Fc-CLEC2(ECD) treatment improves cytokine profiles and increases both the M2 macrophage population and the genes involved in the oxidation of lipid metabolism in the liver. These data reveal a previously unidentified role for CLEC2 as a regulator of macrophage polarity, and establish CLEC2 as a promising therapeutic target for treatment of diabetes and liver disease.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Lectinas Tipo C
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Metabolismo de los Lípidos
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Glucosa
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Macrófagos del Hígado
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
EBioMedicine
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos