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

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)103-109
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume438
Issue number1
DOIs
Publication statusPublished - Aug 16 2013

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T-cells
Macrophages
Cytotoxic T-Lymphocytes
Immunotherapy
Insulin Resistance
Adipose Tissue
Obesity
Insulin
Polarization
Tissue
Antigens
Subcutaneous Fat
CCAAT-Enhancer-Binding Proteins
Inflammation
Arginase
Peroxisome Proliferator-Activated Receptors
Adiponectin
High Fat Diet
Chemokines
Nutrition

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues. / Fujii, Masakazu; Inoguchi, Toyoshi; Batchuluun, Battsetseg; Sugiyama, Naonobu; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi.

In: Biochemical and Biophysical Research Communications, Vol. 438, No. 1, 16.08.2013, p. 103-109.

Research output: Contribution to journalArticle

Fujii, Masakazu ; Inoguchi, Toyoshi ; Batchuluun, Battsetseg ; Sugiyama, Naonobu ; Kobayashi, Kunihisa ; Sonoda, Noriyuki ; Takayanagi, Ryoichi. / CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues. In: Biochemical and Biophysical Research Communications. 2013 ; Vol. 438, No. 1. pp. 103-109.
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