Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2766-2779
Number of pages14
JournalCell Reports
Volume18
Issue number11
DOIs
Publication statusPublished - Mar 14 2017

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Glucose Intolerance
Cell adhesion
Myeloid Cells
Cell Adhesion
Liver
Hepatocytes
Obesity
Integrin alpha4beta1
Glucose
Endothelial cells
Metabolism
Cells
Stromal Cells
Cell Communication
Nutrition
Endothelial Cells
Infiltration
Blood
Gluconeogenesis
Fats

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance. / Miyachi, Yasutaka; Tsuchiya, Kyoichiro; Komiya, Chikara; Shiba, Kumiko; Shimazu, Noriko; Yamaguchi, Shinobu; Deushi, Michiyo; Osaka, Mizuko; Inoue, Kouji; Sato, Yuta; Matsumoto, Sayaka; Kikuta, Junichi; Wake, Kenjiro; Yoshida, Masayuki; Ishii, Masaru; Ogawa, Yoshihiro.

In: Cell Reports, Vol. 18, No. 11, 14.03.2017, p. 2766-2779.

Research output: Contribution to journalArticle

Miyachi, Y, Tsuchiya, K, Komiya, C, Shiba, K, Shimazu, N, Yamaguchi, S, Deushi, M, Osaka, M, Inoue, K, Sato, Y, Matsumoto, S, Kikuta, J, Wake, K, Yoshida, M, Ishii, M & Ogawa, Y 2017, 'Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance', Cell Reports, vol. 18, no. 11, pp. 2766-2779. https://doi.org/10.1016/j.celrep.2017.02.039
Miyachi, Yasutaka ; Tsuchiya, Kyoichiro ; Komiya, Chikara ; Shiba, Kumiko ; Shimazu, Noriko ; Yamaguchi, Shinobu ; Deushi, Michiyo ; Osaka, Mizuko ; Inoue, Kouji ; Sato, Yuta ; Matsumoto, Sayaka ; Kikuta, Junichi ; Wake, Kenjiro ; Yoshida, Masayuki ; Ishii, Masaru ; Ogawa, Yoshihiro. / Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance. In: Cell Reports. 2017 ; Vol. 18, No. 11. pp. 2766-2779.
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AU - Shiba, Kumiko

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AU - Deushi, Michiyo

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AU - Inoue, Kouji

AU - Sato, Yuta

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