• J. Surg. Res. · Jun 2014

    Pioglitazone attenuates lung injury by modulating adipose inflammation.

    • Masahiko Kutsukake, Takeshi Matsutani, Kazuhiro Tamura, Akihisa Matsuda, Makoto Kobayashi, Eiichi Tachikawa, and Eiji Uchida.
    • Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
    • J. Surg. Res. 2014 Jun 15;189(2):295-303.

    BackgroundPioglitazone modulates adipocyte differentiation and enhances adiponectin promoter activity to increase plasma adiponectin levels. We investigated the effects of pioglitazone on cecal ligation and puncture (CLP)-induced visceral-adipose-tissue inflammation and lung injury in mice.Materials And MethodsEight-wk-old male mice were assigned to three groups: (1) a sham-operated control group, (2) a CLP group, and (3) a pioglitazone-treated CLP group. Pioglitazone (10 mg/kg) was injected intraperitoneally for 7 d. Serum, lung, and visceral adipose tissue were collected 24 h after surgery. Tumor necrosis factor α (TNF-α) levels in peritoneal lavage fluid were measured by an enzyme-linked immunosorbent assay, and TNF-α and interleukin 6 messenger RNA (mRNA) expression levels in visceral adipose tissue were quantified by real-time polymerase chain reaction. Lung tissue specimens were stained with hematoxylin-eosin, and the terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling method was used to evaluate tissue damage.ResultsTNF-α levels in peritoneal lavage fluid were significantly higher in the CLP group than in the sham group. TNF-α levels in the pioglitazone-treated CLP group were significantly lower than those in the CLP group. TNF-α and interleukin 6 mRNA expression levels of visceral adipose tissue were significantly higher in the CLP group than in the sham group. Pioglitazone treatment decreased the mRNA expression levels of these cytokines compared with the respective values in the CLP group. Histopathologic analysis of lung tissue revealed significantly increased numbers of terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling-positive cells in the CLP group compared with the sham group.ConclusionsPioglitazone effectively prevents lung injury caused by CLP-induced sepsis by maintaining the anti-inflammatory status of visceral adipose tissue.Copyright © 2014 Elsevier Inc. All rights reserved.

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