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Simultaneous Quantitation of Lipid and Apo‐Protein Synthesis: Diet‐Mediated Reduction in De Novo Lipogenesis is Associated with a Stimulation of ApoB and A1 Production In Vivo
Author(s) -
Previs Stephen,
Zhou Haihong,
Herath Kithsiri,
Xie Dan,
CastroPerez Jose,
Wagner David,
Kelley David
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.389.7
Subject(s) - apolipoprotein b , lipogenesis , fatty acid synthesis , in vivo , cholesterol , chemistry , lipid metabolism , biochemistry , endocrinology , fatty acid , medicine , biology , microbiology and biotechnology
We recently demonstrated the ability to simultaneously quantify lipid and protein flux in vivo using oral D 2 O dosing. The uniqueness of using D 2 O is the rapid equilibration with total body water, use of oral and not intravenous dosing, and ease to measure the true precursor enrichment (either plasma, urine, or saliva). To examine whether dietary modulation of de novo fatty acid and cholesterol synthesis would lead to parallel changes in apoB and/or A1 production, non‐human primates were either fed a standard carbohydrate‐based diet or a high‐fat, high‐cholesterol diet for several months. Lipid and protein kinetics were studied by giving a single oral bolus of D2O and sampling blood for ~ 96 hours thereafter. The dietary perturbation altered the plasma lipid profiles. The analyses of lipid labeling (measured via GC‐IRMS) demonstrated a marked suppression of fatty acid and cholesterol synthesis with high‐fat feeding. Despite these changes we observed a substantial increase in both apoB and A1 synthesis (measured via LC‐MS). In total, we demonstrate that diet‐induced modulation of pathways involving de novo lipid synthesis do not necessarily translate into a comparable protein‐flux phenotype. Our data suggest that the dietary lipid, as compared to de novo synthesized lipid, has a pronounced effect on circulating apo‐protein flux. The methodology applied here can be readily adapted for studies in other pre‐clinical models (e.g. rodents) as well as applied in humans. This protocol design provides a translational biomarker approach for interrogating modulations that affect dyslipidemia.