Role of mesenteric fat in inflammatory bowel diseases

• Project/Area Number: 26460961
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: The University of Tokyo
• Principal Investigator: Kobayashi Yuka 東京大学, 医学部附属病院, 特任臨床医 (80724658)
• Co-Investigator(Kenkyū-buntansha): 平田 喜裕 東京大学, 医学部附属病院, 助教 (10529192) ; 木下 裕人 東京大学, 医学部附属病院, 助教 (50645322)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 炎症性腸疾患 / 腸間膜脂肪組織 / 実験腸炎モデル

Outline of Final Research Achievements

In order to investigate the roles of mesenteric fat in inflammatory bowel diseases, we used experimental colitis models with adipocyte specific genetically engineered mice. In DSS induced colitis model, marked inflammatory cell infiltration was seen in the mesenteric fat tissue, and NFκB activity was elevated in adipocytes in the mesenteric fat. We tried to investigate the role of NFκB signaling in adipocytes in experimental colitis using adipocyte specific IKKβ deficient mice. However, we did not reveal any phenotypic difference from control mice in several experimental systems, including DSS induced colitis model, DSS induced colitis after 8 weeks of high fat diet, and AOM/DSS colitis associated cancer model. We also tried to investigate the role of autophagy in adipocytes in experimental colitis using adipocyte specific ATG5 deficient mice. However, Fabp4-Cre;Atg5 flox/flox mice were very difficult to breed and we could not obtain enough animals to perform necessary experiments.