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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Hesse, Deike Radloff, Katrin Jaschke, Alexander Lagerpusch, Merit Chung, Bomee Tailleux, Anne Staels, Bart Schürmann, Annette |
| Description | Country affiliation: Germany Author Affiliation: Hesse D ( Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, D-14558 Nuthetal, Germany.) |
| Abstract | The liver is a major organ in whole body lipid metabolism and malfunctioning can lead to various diseases including dyslipidemia, fatty liver disease, and type 2 diabetes. Triglycerides and cholesteryl esters are packed in the liver as very low density lipoproteins (VLDLs). Generation of these lipoproteins is initiated in the endoplasmic reticulum and further maturation likely occurs in the Golgi. ADP-ribosylation factor-related protein 1 (ARFRP1) is a small trans-Golgi-associated guanosine triphosphatase (GTPase) that regulates protein sorting and is required for chylomicron lipidation and assembly in the intestine. Here we show that the hepatocyte-specific deletion of Arfrp1 (Arfrp1(liv-/-)) results in impaired VLDL lipidation leading to reduced plasma triglyceride levels in the fasted state as well as after inhibition of lipoprotein lipase activity by Triton WR-1339. In addition, the concentration of ApoC3 that comprises 40% of protein mass of secreted VLDLs is markedly reduced in the plasma of Arfrp1(liv-/-) mice but accumulates in the liver accompanied by elevated triglycerides. Fractionation of Arfrp1(liv-/-) liver homogenates reveals more ApoB48 and a lower concentration of triglycerides in the Golgi compartments than in the corresponding fractions from control livers. In conclusion, ARFRP1 and the Golgi apparatus play an important role in lipoprotein maturation in the liver by influencing lipidation and assembly of proteins to the lipid particles. |
| File Format | HTM / HTML |
| ISSN | 00222275 |
| e-ISSN | 15397262 |
| DOI | 10.1194/jlr.M040089 |
| Journal | The Journal of Lipid Research |
| Issue Number | 1 |
| Volume Number | 55 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2014-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Biochemistry Adp-ribosylation Factors Physiology Lipoproteins, Vldl Metabolism Liver Protein Processing, Post-translational Trans-golgi Network Enzymology Animals Apolipoprotein A-i Secretion Endoplasmic Reticulum Lipogenesis Lipoproteins, Hdl Mice Mice, Inbred C57bl Mice, Knockout Triglycerides Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Endocrinology |
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