CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues.
Biochem Biophys Res Commun
; 438(1): 103-9, 2013 Aug 16.
Article
en En
| MEDLINE
| ID: mdl-23872146
ABSTRACT
It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent.
Palabras clave
AIM; AUC; Anti-inflammation; CTLA-4lg; HFD; IPGT; ITT; Insulin resistance; MCP; Macrophage polarization; NCD; Obesity; RA; SVF; apoptosis inhibitor of macrophage; area under the curve; cytotoxic T-lymphocyte-associated antigen-4IgG1; high fat diet; insulin tolerance test; intraperitoneal glucose tolerance test; monocyte chemotactic protein; normal chow diet; rheumatoid arthritis; stromal vascular fraction
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Resistencia a la Insulina
/
Tejido Adiposo
/
Antígeno CTLA-4
/
Inmunoterapia
/
Macrófagos
/
Obesidad
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2013
Tipo del documento:
Article
País de afiliación:
Japón