Nirav K Desai1, Esther M Ooi2, Paul D Mitchell3, Jeremy Furtado4, Frank M Sacks5. 1. Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 2. School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3. Clinical Research Center, Boston Children's Hospital, Boston, MA, USA. 4. Department of Nutrition, Harvard School of Public Health and Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. 5. Department of Nutrition, Harvard School of Public Health and Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: fsacks@hsph.harvard.edu.
Abstract
OBJECTIVE: To characterize human triglyceride-rich lipoproteins (TRL) with and without apoA-II and to study their metabolism in vivo. METHODS: Plasma from 11 participants on a controlled diet given a bolus infusion of [D5]l-phenylalanine to label apoB was combined into four pools and applied to anti-apoA-II immunoaffinity columns. Fractions with and without apoA-II were separated into VLDL and IDL by ultracentrifugation; lipids and apolipoproteins were measured. For kinetic measurements, apoB was isolated and hydrolyzed to the constituent amino acids. Tracer enrichment was measured by GCMS. Metabolic rates were determined by SAAM-II. RESULTS: VLDL and IDL with apoA-II comprised 7% and 9% of total VLDL and IDL apoB respectively. VLDL with apoA-II was enriched in apoC-III, apoE, and cholesterol compared to VLDL without apoA-II. Mean apoB FCR of VLDL with apoA-II was significantly lower than for VLDL without apoA-II (2.80 ± 0.96 pools/day v.s. 5.09 ± 1.69 pools/day, P = 0.009). A higher percentage of VLDL with apoA-II was converted to IDL than was cleared from circulation, compared to VLDL without apoA-II (96 ± 8% vs. 45 ± 22%; P = 0.007). The rate constants for conversion of VLDL to IDL were similar for VLDL with and without apoA-II. Thus, a very low rate constant for clearance accounted for the lower FCR of VLDL with apoA-II. CONCLUSION: VLDL with apoA-II represents a small pool of VLDL particles that has a slow FCR and is predominantly converted to IDL rather than cleared from the circulation.
OBJECTIVE: To characterize humantriglyceride-rich lipoproteins (TRL) with and without apoA-II and to study their metabolism in vivo. METHODS: Plasma from 11 participants on a controlled diet given a bolus infusion of [D5]l-phenylalanine to label apoB was combined into four pools and applied to anti-apoA-II immunoaffinity columns. Fractions with and without apoA-II were separated into VLDL and IDL by ultracentrifugation; lipids and apolipoproteins were measured. For kinetic measurements, apoB was isolated and hydrolyzed to the constituent amino acids. Tracer enrichment was measured by GCMS. Metabolic rates were determined by SAAM-II. RESULTS:VLDL and IDL with apoA-II comprised 7% and 9% of total VLDL and IDL apoB respectively. VLDL with apoA-II was enriched in apoC-III, apoE, and cholesterol compared to VLDL without apoA-II. Mean apoB FCR of VLDL with apoA-II was significantly lower than for VLDL without apoA-II (2.80 ± 0.96 pools/day v.s. 5.09 ± 1.69 pools/day, P = 0.009). A higher percentage of VLDL with apoA-II was converted to IDL than was cleared from circulation, compared to VLDL without apoA-II (96 ± 8% vs. 45 ± 22%; P = 0.007). The rate constants for conversion of VLDL to IDL were similar for VLDL with and without apoA-II. Thus, a very low rate constant for clearance accounted for the lower FCR of VLDL with apoA-II. CONCLUSION:VLDL with apoA-II represents a small pool of VLDL particles that has a slow FCR and is predominantly converted to IDL rather than cleared from the circulation.
Authors: J C Escolà-Gil; J Julve; A Marzal-Casacuberta; J Ordóñez-Llanos; F González-Sastre; F Blanco-Vaca Journal: J Lipid Res Date: 2000-08 Impact factor: 5.922
Authors: J Julve; J C Escolà-Gil; A Marzal-Casacuberta; J Ordóñez-Llanos; F González-Sastre; F Blanco-Vaca Journal: Biochim Biophys Acta Date: 2000-11-15
Authors: Lawrence W Castellani; Cara N Nguyen; Sarada Charugundla; Michael M Weinstein; Chau X Doan; William S Blaner; Nuttaporn Wongsiriroj; Aldons J Lusis Journal: J Biol Chem Date: 2007-12-26 Impact factor: 5.157
Authors: Carlos O Mendivil; Chunyu Zheng; Jeremy Furtado; Julian Lel; Frank M Sacks Journal: Arterioscler Thromb Vasc Biol Date: 2009-11-12 Impact factor: 8.311
Authors: John D Bagdade; Bernd Jilma; Lisa C Hudgins; Petar Alaupovic; Carrie E McCurdy Journal: Lipids Health Dis Date: 2018-05-28 Impact factor: 3.876