Roles for Cell-Cell Adhesion and Contact in Obesity-Induced Hepatic Myeloid Cell Accumulation and Glucose Intolerance
| Autor: | Masayuki Yoshida, Kenjiro Wake, Masaru Ishii, Junichi Kikuta, Sayaka Matsumoto, Mizuko Osaka, Kouji Inoue, Yoshihiro Ogawa, Kumiko Shiba, Kyoichiro Tsuchiya, Chikara Komiya, Yasutaka Miyachi, Michiyo Deushi, Noriko Shimazu, Shinobu Yamaguchi, Yuta Sato |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male obesity Myeloid Cell Mice Obese Integrin alpha4beta1 neutrophils Cell Movement insulin resistance Leukocytes Myeloid Cells lcsh:QH301-705.5 Notch signaling Receptors Notch diabetes Up-Regulation macrophages medicine.anatomical_structure Liver monocytes Infiltration (medical) Signal Transduction medicine.medical_specialty Stromal cell liver sinusoidal endothelial cells Carbohydrate metabolism Biology General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Internal medicine Glucose Intolerance medicine Cell Adhesion Animals Cell adhesion Antibodies Blocking Gluconeogenesis Endothelial Cells Metabolism medicine.disease Mice Inbred C57BL 030104 developmental biology Endocrinology Glucose Gene Expression Regulation lcsh:Biology (General) inflammation Hepatocytes Cell Adhesion Molecules |
| Zdroj: | Cell Reports, Vol 18, Iss 11, Pp 2766-2779 (2017) |
| ISSN: | 2211-1247 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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