Study of a novel NF-kappaB-regulating protein, Nucling, in the development of non-alcoholic fatty liver diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460388
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Tokushima Bunri University (2014-2015); The University of Tokushima (2013)
• Principal Investigator: SAKAI TAKASHI 徳島文理大学, その他の研究科, 教授 (80284321)
• Co-Investigator(Kenkyū-buntansha): FUKUI Kiyoshi 徳島大学, 疾患酵素学研究センター, 教授 (00175564)
• Research Collaborator: Dang Huy Van ; Pham Tuan Anh ; Tran Diem Hong ; Kim Sun Mi
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: NAFLD / Nucling / NF-κB / metabolic syndrome / insulin resistance

Outline of Final Research Achievements

Nonalcoholic fatty liver disease, NAFLD, is a cause of a fatty liver not due to excess alcohol use, which is related to insulin resistance and metabolic abnormalities. Here, we found that Nucling-KO mice develop hallmark features of NAFLD. We hypothesized that these metabolic changes might correlate with the accumulation of oxidative stress in liver, and malfunction of insulin regulation in pancreas. Nucling deficiency promoted the accumulation of reactive oxygen species in liver of mice. High fat diet revealed dysregulation of insulin expression in the Nucling-KO mice. We also found that glucose-induced insulin up-regulation requires NF-κB activation, which is dysregulated in Nucling-KO mice. These results suggest that defect of the Nucling-NF-κB system promoted the malfunction of insulin transcription resulted in development of metabolic disorders including NAFLD. In conclusion, we propose that NF-κB signal is important for the homeostatic regulation of insulin transcription.

Free Research Field

病態生理学