Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance
Obesity promotes infiltration of inflammatory cells into various tissues, leading to parenchymal and stromal cell interaction and development of cellular and organ dysfunction. Liver sinusoidal endothelial cells (LSECs) are the first cells that contact portal blood cells and substances in the liver,...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717302371 |
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doaj-e33dfdfd143c4d5699fe6ff694e6f159 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yasutaka Miyachi Kyoichiro Tsuchiya Chikara Komiya Kumiko Shiba Noriko Shimazu Shinobu Yamaguchi Michiyo Deushi Mizuko Osaka Kouji Inoue Yuta Sato Sayaka Matsumoto Junichi Kikuta Kenjiro Wake Masayuki Yoshida Masaru Ishii Yoshihiro Ogawa |
| spellingShingle |
Yasutaka Miyachi Kyoichiro Tsuchiya Chikara Komiya Kumiko Shiba Noriko Shimazu Shinobu Yamaguchi Michiyo Deushi Mizuko Osaka Kouji Inoue Yuta Sato Sayaka Matsumoto Junichi Kikuta Kenjiro Wake Masayuki Yoshida Masaru Ishii Yoshihiro Ogawa Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance Cell Reports insulin resistance inflammation obesity diabetes macrophages neutrophils monocytes Notch signaling liver sinusoidal endothelial cells |
| author_facet |
Yasutaka Miyachi Kyoichiro Tsuchiya Chikara Komiya Kumiko Shiba Noriko Shimazu Shinobu Yamaguchi Michiyo Deushi Mizuko Osaka Kouji Inoue Yuta Sato Sayaka Matsumoto Junichi Kikuta Kenjiro Wake Masayuki Yoshida Masaru Ishii Yoshihiro Ogawa |
| author_sort |
Yasutaka Miyachi |
| title |
Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance |
| title_short |
Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance |
| title_full |
Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance |
| title_fullStr |
Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance |
| title_full_unstemmed |
Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance |
| title_sort |
roles for cell-cell adhesion and contact in obesity-induced hepatic myeloid cell accumulation and glucose intolerance |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2017-03-01 |
| description |
Obesity promotes infiltration of inflammatory cells into various tissues, leading to parenchymal and stromal cell interaction and development of cellular and organ dysfunction. Liver sinusoidal endothelial cells (LSECs) are the first cells that contact portal blood cells and substances in the liver, but their functions in the development of obesity-associated glucose metabolism remain unclear. Here, we find that LSECs are involved in obesity-associated accumulation of myeloid cells via VLA-4-dependent cell-cell adhesion. VLA-4 blockade in mice fed a high-fat diet attenuated myeloid cell accumulation in the liver to improve hepatic inflammation and systemic glucose intolerance. Ex vivo studies further show that cell-cell contact between intrahepatic leukocytes and parenchymal hepatocytes induces gluconeogenesis via a Notch-dependent pathway. These findings suggest that cell-cell interaction between parenchymal and stromal cells regulates hepatic glucose metabolism and offers potential strategies for treatment or prevention of obesity-associated glucose intolerance. |
| topic |
insulin resistance inflammation obesity diabetes macrophages neutrophils monocytes Notch signaling liver sinusoidal endothelial cells |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124717302371 |
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doaj-e33dfdfd143c4d5699fe6ff694e6f1592020-11-25T01:56:58ZengElsevierCell Reports2211-12472017-03-0118112766277910.1016/j.celrep.2017.02.039Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose IntoleranceYasutaka Miyachi0Kyoichiro Tsuchiya1Chikara Komiya2Kumiko Shiba3Noriko Shimazu4Shinobu Yamaguchi5Michiyo Deushi6Mizuko Osaka7Kouji Inoue8Yuta Sato9Sayaka Matsumoto10Junichi Kikuta11Kenjiro Wake12Masayuki Yoshida13Masaru Ishii14Yoshihiro Ogawa15Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Life Science and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Life Science and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Anatomy and Histocytology, School of Dental Medicine, Tsurumi University, Yokohama, Kanagawa 230-8501, JapanDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Anatomy and Histocytology, School of Dental Medicine, Tsurumi University, Yokohama, Kanagawa 230-8501, JapanDepartment of Life Science and Bioethics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanDepartment of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, JapanDepartment of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, JapanObesity promotes infiltration of inflammatory cells into various tissues, leading to parenchymal and stromal cell interaction and development of cellular and organ dysfunction. Liver sinusoidal endothelial cells (LSECs) are the first cells that contact portal blood cells and substances in the liver, but their functions in the development of obesity-associated glucose metabolism remain unclear. Here, we find that LSECs are involved in obesity-associated accumulation of myeloid cells via VLA-4-dependent cell-cell adhesion. VLA-4 blockade in mice fed a high-fat diet attenuated myeloid cell accumulation in the liver to improve hepatic inflammation and systemic glucose intolerance. Ex vivo studies further show that cell-cell contact between intrahepatic leukocytes and parenchymal hepatocytes induces gluconeogenesis via a Notch-dependent pathway. These findings suggest that cell-cell interaction between parenchymal and stromal cells regulates hepatic glucose metabolism and offers potential strategies for treatment or prevention of obesity-associated glucose intolerance.http://www.sciencedirect.com/science/article/pii/S2211124717302371insulin resistanceinflammationobesitydiabetesmacrophagesneutrophilsmonocytesNotch signalingliver sinusoidal endothelial cells |