Print Email Facebook Twitter Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids Title Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids Author Kersten, S. Lichtenstein, L. Steenbergen, E. Mudde, K. Hendriks, H.F.J. Hesselink, M.K. Schrauwen, P. Müller, M. TNO Kwaliteit van Leven Publication year 2009 Abstract OBJECTIVE-: Plasma lipoprotein levels are determined by the balance between lipoprotein production and clearance. Recently, angiopoietin-like protein 4 (ANGPTL4) was uncovered as a novel endocrine factor that potently raises plasma triglyceride levels by inhibiting triglyceride clearance. However, very little is known about ANGPTL4 in human. Here we set out to identify physiological determinants of plasma ANGPTL4 levels in humans, focusing on the effect of energy restriction and plasma FFAs. METHODS AND RESULTS-: We developed an ELISA for quantitative measurement of ANGPTL4 in human plasma. Using this assay we found major variations in baseline plasma ANGPTL4 levels between individuals. Within an individual, plasma ANGPTL4 levels remain stable throughout the day but increase significantly in response to long-term fasting, chronic caloric restriction, and endurance exercise. Intralipid injection as well as treatment with a β-adrenergic agonist, both of which lead to elevated plasma FFA levels, increased plasma ANGPTL4 levels compared to control treatment. Fatty acids markedly induced ANGPTL4 gene expression in rat hepatoma FAO cells, human primary myocytes, and mouse intestinal MSIE cells. CONCLUSION-: In conclusion, our results show that plasma ANGPTL4 levels are increased by fasting, caloric restriction, and exercise, which is likely mediated by elevated plasma FFAs. © 2009 American Heart Association, Inc. Subject NutritionBiomedical ResearchANGPTL4Caloric restrictionFree fatty acidsangiopoietinangiopoietin like protein 4beta adrenergic receptor stimulating agentfatty acidunclassified drugANGPTL4 protein, humanAngptl4 protein, mouseantilipemic agentFiaf protein, ratlipid emulsionmessenger RNAsalbutamoladultanimal cellarticleblood samplingcaloric restrictioncell strain HepG2controlled studyenzyme linked immunosorbent assayexercisefatty acid blood levelfemalegene expressiongenetic variabilityhepatoma cellhumanhuman cellhuman experimentintestine cellmalemousemuscle cellnonhumannormal humanpriority journalprotein blood levelratanimalbloodcell cultureclinical trialcontrolled clinical trialgenetic transfectiongeneticsheart muscle cellintestineliver tumormetabolismmiddle agedrandomized controlled trialtimeupregulationAdrenergic beta-AgonistsAdultAlbuterolAngiopoietinsAnimalsAntilipemic AgentsCaloric RestrictionCells, CulturedEnzyme-Linked Immunosorbent AssayExerciseFat Emulsions, IntravenousFatty Acids, NonesterifiedHumansIntestinesLiver NeoplasmsMaleMiceMiddle AgedMyocytes, CardiacRatsRNA, MessengerTime FactorsTransfectionUp-RegulationYoung Adult To reference this document use: http://resolver.tudelft.nl/uuid:51e5ebb0-87bf-45c1-a4b0-f273e6ffdbdc DOI https://doi.org/10.1161/atvbaha.108.182147 TNO identifier 241583 ISSN 1079-5642 Source Arteriosclerosis, Thrombosis, and Vascular Biology, 29 (6), 969-974 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.