Molecular Medicine and Metabolism
Obesity may be viewed as a state of chronic, low-grade inflammation, which plays an important role in the development of the metabolic syndrome. Indeed, unbalanced production of pro- and anti-inflammatory adipocytokines observed in visceral fat obesity plays a critical role in the pathophysiology of the metabolic syndrome. Recent evidence has revealed that adipose tissue in obesity exhibits chronic inflammatory changes, thereby contributing to the pathogenesis of metabolic derangements of multiple organs. We have provided evidence on the molecular mechanisms of how obesity induces adipose tissue inflammation and how adipose tissue inflammation disturbs adipose tissue function, especially focusing on the crosstalk between adipocytes and macrophages. Understanding the role of chronic inflammation in the metabolic syndrome will lead to identification of novel therapeutic strategies to prevent or treat obesity-related diseases such as diabetes, nonalcoholic steatohepatitis, and chronic kidney disease.
- M. Tanaka, M. Saka-Tanaka, K. Ochi, K. Fujieda, Y. Sugiura, T. Miyamoto, H. Kohda, A. Ito, T. Miyazawa, A. Matsumoto, S. Aoe, Y. Miyamoto, N. Tsuboi, S. Maruyama, M. Suematsu, S. Yamasaki, Y. Ogawa, T. Suganami. C-type lectin Mincle mediates cell death–triggered sustained inflammation in acute kidney injury J. Exp. Med. in press, 2020.
- A. Matsumoto, H. Kuwata, S. Kimura, H. Matsumoto, K. Ochi, Y. Moro-oka, A. Watanabe, H. Yamada, H. Ishii, T. Miyazawa, S. Chen, T. Baba, H. Yoshida, T. Nakamura, H. Inoue, Y. Ogawa, M. Tanaka, Y. Miyahara, T. Suganami. Hollow fiber-combined glucose-responsive gel technology as an in vivo electronics-free insulin delivery system. Commun. Biol. 3: 313, 2020.
- M. Kawakubo, M. Tanaka, K. Ochi, A. Watanabe, M. Saka-Tanaka, Y. Kanamori1, N. Yoshioka, S. Yamashita, M. Goto, M. Itoh, I. Shirakawa, S. Kanai, H. Suzuki, M. Sawada, A. Ito, M. Ishigami, M. Fujishiro, H. Arima, Y. Ogawa, T. Suganami. Dipeptidyl peptidase-4 inhibition prevents nonalcoholic steatohepatitis–associated liver fibrosis and tumor development in mice independently of its anti-diabetic effects. Sci. Rep. 10: 983, 2020.
- 4) M. Asakawa, M. Itoh, T. Suganami, T. Sakai, S. Kanai, I. Shirakawa, X. Yuan, T. Hatayama, S. Shimada, Y. Akiyama, K. Fujiu, Y. Inagaki, I. Manabe, S. Yamaoka, T. Yamada, S. Tanaka, Y. Ogawa. Upregulation of cancer-associated gene expression in activated fibroblasts in a mouse model of non-alcoholic steatohepatitis. Sci. Rep. 9: 19601, 2019.
- S. Chen, H. Matsumoto, Y. Moro-oka, M. Tanaka, Y. Miyahara, T. Suganami, A. Matsumoto. Microneedle-array patch fabricated with enzyme-free polymeric components capable of a weekly on-demand insulin delivery. Adv. Funct. Mater. 1807369, 2018. (cover picture of the issue)
- A. Matsumoto, M. Tanaka, H. Matsumoto, K. Ochi, Y. Moro-oka, H. Kuwata, H. Yamada, I. Shirakawa, T. Miyazawa, H. Ishii, K. Kataoka, Y. Ogawa, Y. Miyahara, T. Suganami. Synthetic “smart-gel” provides glucose-responsive insulin delivery in diabetic mice. Sci. Adv. 3: eaaq0723, 2017. (cover picture of the issue)
- M. Itoh, T. Suganami, H. Kato, S. Kanai, I. Shirakawa, T. Sakai, T. Goto, M. Asakawa, I. Hidaka, H. Sakugawa, K. Ohnishi, Y. Komohara, K. Asano, I. Sakaida, M. Tanaka, Y. Ogawa. CD11c-positive resident macrophages drive hepatocyte death-triggered liver fibrosis in a murine model of non-alcoholic steatohepatitis. JCI Insight 2: e92902, 2017.
- M. Tanaka, K. Ikeda, T. Suganami, C. Komiya, K. Ochi, I. Shirakawa, M. Hamaguchi, S. Nishimura, I. Manabe, T. Matsuda, K. Kimura, H. Inoue, Y. Inagaki, S. Aoe, S. Yamasaki, Y. Ogawa. Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis. Nat. Commun. 5: 4982, 2014.
- Y. Iwasaki, T. Suganami, R. Hachiya, I. Shirakawa, M. Kim-Saijo, M. Tanaka, M. Hamaguchi, T. Takai-Igarashi, M. Nakai, Y. Miyamoto, Y. Ogawa. Activating transcription factor 4 links metabolic stress to interleukin-6 expression in macrophages. Diabetes 63: 152-161, 2014. (highlighted in commentary)
- M. Ichioka, T. Suganami, N. Tsuda, I. Shirakawa, Y. Hirata, N. Satoh-Asahara, Y. Shimoda, M. Tanaka, M. Kim-Saijo, Y. Miyamoto, Y. Kamei, M. Sata, Y. Ogawa. Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. Diabetes 60: 819-826, 2011.
- M. Tanaka, T. Suganami, M. Kim-Saijo, C. Toda, M. Tsuiji, K. Ochi, Y. Kamei, Y. Minokoshi, Y. Ogawa. Role of central leptin signaling in the starvation-induced alteration of B cell development. J. Neurosci. 31: 8373-8380, 2011.
- M. Itoh, T. Suganami, N. Nakagawa, M. Tanaka, Y. Yamamoto, Y. Kamei, S. Terai, I. Sakaida, Y. Ogawa. Melanocortin-4 receptor-deficient mice as a novel mouse model of non-alcoholic steatohepatitis.Am. J. Pathol. 179: 2454-2463, 2011.