[대학원 생명과학과 세미나 안내]
연사 : 박상원 교수(Harvard Medical School)
연제 : The insulin signaling pathway in obesity and type 2 diabetes
일시 : 2017년 2월 8일 (수) 오후 4시30분
장소 : 하나과학관 A동 207호
초청교수 : 최상윤 교수
Abstract
Endoplasmic Reticulum (ER) stress plays crucial roles in the development of various metabolic disorders such as insulin resistance, diabetes, and obesity. X-Box binding protein 1 (XBP1) is an active transcription factor in the regulation of ER stress signaling and unfolded protein response (UPR). Deletion of an XBP1 allele leads to the development of obesity and insulin resistance. To date, our understanding of the regulation of XBP1 in metabolic processes is still limited. In our current work, we demonstrate that bromodomain containing protein 7 (BRD7) regulates glucose homeostasis by increasing the nuclear translocation and activity of XBP1s through its interaction with the regulatory subunits of phosphatidyl-inositol3kinase (PI3K), p85s. We show that BRD7 protein levels are significantly reduced in the liver of genetically obese and high fat diet (HFD)-induced obese mouse models. Over-expression of BRD7 in the liver of ob/ob and HFD fed mice ameliorates hyperglycemia and glucose intolerance through increasing the nuclear translocation of XBP1s and decreasing ER stress levels. Furthermore, our data show that homozygous BRD7 knockout mice are embryonic lethal and partial knockdown of BRD7 gene display mild changes in glucose metabolism. Of interest, heterozygous BRD7 knockout mice display increased body weights and blockage in the nuclear translocation of XBP1s. Our results provide the first evidence that BRD7, which was originally reported as a tumor suppressor, is involved in the regulation of UPR and glucose metabolism.