Details

Autor(en) / Beteiligte

• Fujii, Masakazu
• Inoguchi, Toyoshi
• Batchuluun, Battsetseg
• Sugiyama, Naonobu
• Kobayashi, Kunihisa
• Sonoda, Noriyuki
• Takayanagi, Ryoichi

Titel

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues

Ist Teil von

• Biochemical and biophysical research communications, 2013-08, Vol.438 (1), p.103-109

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• •CTLA-4Ig completely alleviates HFD-induced insulin resistance.•CTLA-4Ig reduces epididymal and subcutaneous fat tissue weight and adipocyte size.•CTLA-4Ig alters ATM polarization from inflammatory M1 to anti-inflammatory M2.•CTLA-4Ig may lead to a novel anti-obesity/inflammation/insulin resistance agent.•We identified the mechanism of the novel favorable effects of CTLA-4lg. 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.