ER stress-mediated FoxO1 induces impaired insulin signaling and hepatic steatosis in aging process

• 발행기관: 한국노년학회
• 저자명: Sugyeong Ha Dae Hyun Kim Yeo Jin Park Eun jin Bang Min Kyung Hyun A Kyoung Lee Hae Young Chung
• 간행물 정보: 『한국노년학회 학술대회 논문집』2017년 한국노인과학학술대회, 263~263쪽, 전체 1쪽
• 주제분류: 사회과학 > 사회복지학
• 파일형태: PDF
• 발행일자: 2017.11.03

영문 초록

Dysregulated forkhead box O1 (FoxO1) is involved in hepatic insulin resistance with aging in rat. It has been reported that endoplasmic reticulum (ER) stress causes de novo lipogenesis by increasing hepatic insulin resistance. However, the precise role of FoxO1 in the ERstress-inducedinsulinresistanceandhepaticlipogenesishas not been elucidated. We demonstrate that FoxO1 transcription factor regulates PPARγ-induced lipid accumulation under ER stress conditions in aged rat. We also investigated the effect of FoxO1 on lipid metabolism in aged liver. Here, we showed increased glucose tolerance and hepatic steatosis in aged liver. In addition, hepatic insulin signaling was increased and induced activation of FoxO1, which was negatively regulated by IRS/Akt. The protein level of PPARγ, a lipogenic transcription factor, was increased in aged liver. Therefore, we further investigated whether FoxO1 mediates PPARγ-induced hepatic steatosis by insulin signaling by ER stress in AC2F hepatocytes. Interestingly, FoxO1 adenovirus notably increased mRNA expression of genes related to lipogenesis. Furthermore, FoxO1 regulated binding of the PPARγ promoter and PPARγ transcriptional activity in AC2F hepatocytes, which might be mediated to induce hepatic steatosis in aging. We conclude that ER stress-mediated FoxO1 induces hepatic steatosis, in part, by PPARγ activation and thereby increasing lipogenic gene transcription.

키워드

FoxO1 PPARa/β/γ ER stress Insulin resistance Steatosis Aging