Mechanisms of hepatic steatosis and insulin resistance induced by sleep deprivation in mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16213
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Toho University
• Principal Investigator: SHIGIYAMA Fumika 東邦大学, 医学部, 助教 (70808188)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 2型糖尿病 / 睡眠障害 / 脂肪肝

Outline of Final Research Achievements

The aim of this study was to investigate the effect of down-regulation of hepatic elovl3 on hepatic lipid accumulation and glucose metabolism during sleep deprivation. In order to suppress the expression of elovl3 in liver, elovl3 specific siRNA was injected through tail vein to 13-weeks old C57BL/6J mice (elovl3 group), and non-coding siRNA was injected to control mice (control group). After single 6 hours sleep deprivation in fasted and moving-restricted condition, hepatic triglyceride content was significantly reduced in elovl3 group compared to control group(P<0.01). Although no significant difference was observed regarding hepatic gluconeogenesis assessed by pyruvate challenge test, the blood glucose level at 30 minutes in intraperitoneal glucose tolerance test was significantly lower in elovl3 group(P<0.05). These data suggest that the suppression of elovl3 may ameliorate the sleep deprivation induced hepatic steatosis, but its effects on glucose metabolism was limited.

Free Research Field

糖尿病・代謝・内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究成果から、マウス肝臓においてElovl3の発現を抑制することで睡眠障害により生じる肝脂肪蓄積が減少し耐糖能が改善することが明らかとなった。これまで、睡眠障害による糖代謝悪化のメカニズムについて、インスリン抵抗性の関与が示唆されてきたが、未解明の部分も多く具体的な介入法は確立されていなかった。睡眠障害により発症・増悪する2型糖尿病に対して、睡眠薬に頼らない、汎用性のある新規治療ターゲットとして、肝臓でのElovl3の糖・脂質代謝への役割の一部が解明されたことで、ヒトの日常生活における睡眠障害による糖代謝異常への応用も見据えた効果的な治療法の確立に貢献しうると期待される。