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Inverse relationship between very low‐density lipoprotein (VLDL) ceramides, diacylglycerols, and triacylglycerols in human hepatic lipid accumulation
Author(s) -
Mucinski Justine M,
SyedAbdul Majid Mufaqam,
Garrett Timothy J,
Parks Elizabeth J
Publication year - 2019
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.2019.33.1_supplement.lb567
Subject(s) - very low density lipoprotein , medicine , endocrinology , apolipoprotein b , chemistry , triglyceride , cholesterol , lipoprotein , biology
Ceramides (CER), along with other lipotoxic lipids (diacylglycerols, DAG and triacylglycerols, TG), have been implicated in the development and progression of nonalcoholic fatty liver disease (NAFLD). No study to date has measured CER, DAG, and TG concentrations in VLDL with relation to liver fat content. Twelve male subjects with characteristics that put them at risk for NAFLD (mean±SD, age 42.1±5.4y, BMI 37.8±3.5 kg/m 2 , ALT 45±21 U/L) were studied. VLDL particles were isolated in the fasted state and lipid species measured via UHPLC‐MS/MS analysis. VLDL‐apoB100 was measured by ELISA and intrahepatic triglycerides (IHTG) by MRS. Total VLDL‐CER concentrations were positively correlated with both VLDL‐TG (r = 0.572, P = 0.004) and VLDL‐apoB100 (r = 0.557, P = 0.005). Total VLDL‐DAG concentrations were significantly positively correlated with VLDL‐apoB100 (r = 0.724, P < 0.001), tended to correlate with VLDL‐TG (r = 0.263, P = 0.088) but were most strongly correlated with VLDL‐CER (figure, r = 0.860, P < 0.001). With regard to IHTG, both plasma VLDL‐CER and VLDL‐TG were negatively correlated with liver fat (r = −0.447, P = 0.018 and r = −0.551, P = 0.006, respectively), while the relationship between IHTG and VLDL‐DAG was more modest (r = −0.290, P = 0.071). These data suggest that CER, DAG, and TG are packaged together in the liver and secreted simultaneously on VLDL particles. A less likely scenario is that CER or DAG are added to VLDL after the particles have been secreted into the plasma. These data support the concept that hepatic secretion rates of CER and TG, and to some extent, DAG, are potentially beneficial physiological processes that lower excess hepatic lipid accumulation in metabolic syndrome to support overall liver health. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .