Angiopoietin-like protein 8 (betatrophin) is a stress-response protein that down-regulates expression of adipocyte triglyceride lipase |
| |
| Affiliation: | 1. Department of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA;2. Center for Stem Cell and Regenerative Medicine, The Second Hospital of Shandong University, Jinan 250012, PR China;3. Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA;4. Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA;1. Department of Surgery, Kaohsiung Veterans General Hospital, No. 386, Ta-chung 1st Road, Kaohsiung, 813, Taiwan;2. Department of Biological Sciences, National Sun Yat-Sen University, No. 70, Lien-Hai Road, Kaohsiung, 804, Taiwan;3. Institute of Emergency and Critical Care Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan;4. Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City, 112, Taiwan |
| |
| Abstract: | AimAtypical angiopoietin-like 8 (ANGPTL8), also known as betatrophin, is known to regulate lipid metabolism. However, its mechanism of action remains elusive.MethodsHepG2, 3T3-L1, and NIT-1 cells were cultured in amino acid-complete MEM or histidine-free MEM to detect ANGPTL8 expression. The three cell types were treated with or without recombinant ANGPTL8 to investigate its role in lipid metabolism. Hydrodynamic tail vein gene delivery was also used to examine the role of ANGPTL8 in mice.ResultsANGPTL8 is significantly up-regulated in amino acid-deprived cultured cells in vitro. The activation of ANGPTL8 gene transcription was mediated through the RAS/c-RAF/MAPK signaling pathway rather than the general GCN2/ATF4 pathways. ANGPTL8 activated the ERK signal transduction pathway in hepatocytes, adipocytes, and pancreatic β-cells, up-regulating early growth response transcription factor (Egr1) and down-regulating adipose triglyceride lipase (ATGL).ConclusionANGPTL8 is a stress-response protein that regulates fat metabolism by suppressing ATGL expression, revealing a mechanistic connection between ANGPTL8 and lipid homeostasis in mammalian cells. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
