LPA levels above 30mg/dL are considered an important risk factor

LPA levels above 30mg/dL are considered an important risk factor for CVD. Conversely, LPA levels inversely correlate with the incidence of diabetes and HOMA-IR (Cardiovasc Diabetol, 2012). We therefore aimed to assess the impact of an oral 4 week 150g/day FC on hepatic lipid metabolism reflected by total hepatic lipid content (HLC), fatty acid saturation and phosphorous metabolites (PM; indicating hepatic energy metabolism), and

glucose homeostasis. Moreover, we aimed to explore the role of LPA as potential biomarker predicting hepatic sensibility to fructose induced (lipo)toxicity. Methods: Ten healthy volunteers were enrolled in a pilot study (m: f=5: 5; median age 24.5 (21-37)). HLC (CH2 fraction of total signal), unsaturation- (UI), saturation- (SI=1-UI) and polyunsaturation indices (PUI) were determined R788 by single voxel 3.0-T 1H-, PM by 31P-MRS. BMI was assessed Z-VAD-FMK ic50 clinically. Blood was collected at days 1, 14 and 28 for routine laboratory analysis, LPA at baseline and fasted glucose. Results: Mean BMI was 21.11 ± 2.68 (SD) kg/m^2 and increased after FC (21.51 ± 2.77; p<0.001). UIs increased from mean 0.175 ± 0.087 to 0.226 ± 0.066 (p=0.034 one-tailed; large effect size r=0.568). Similarly, fasting glucose levels increased (mean 83.2mg/dL ± 8.37 to 88.4 ± 5.48, p=0.035). Notably, total HLC, PUIs, PM, ALT, AST and yGt remained unchanged (p>0.05). Analysis

of responders to FC (FCR; n=6) as reflected by increased total N-acetylglucosamine-1-phosphate transferase HLC (as potential indicator for lipid partitioning of potentially toxic lipid intermediates as neutral TG) versus non-responders (FCNR; n=4) revealed αATP depletion in FCNR (mean 3.003 ± 2.07 to 1.67 ± 0.413; p=0.034 onetailed). In FCR reflected by increased UI (n=7) γATP depletion was

observed (mean 2.18 ± 0.71 to 1.51 ± 0.4; p=0.036). Notably, baseline LPA levels inversely correlated with total HLC following FC (r=-0.801; p=0.004; r^2=0.652; non-linear fit: r^2=0.594) and delta-αATP (r=-0.652; p=0.039). Conclusions: MRS is feasible to detect slight changes in intrahepatic lipid composition after FC in healthy young volunteers. Changes in fatty acid saturation indices may occur earlier compared to other well established markers of liver damage. Moreover, serum LPA may also serve as a novel biomarker to differentiate between individuals at increased risk for NAFLD, particularly under fructose challenge. Approaches aimed at lowering LPA to counteract CVD risk should also consider potential interactions with hepatic lipid content and partitioning. Disclosures: Michael Trauner – Advisory Committees or Review Panels: MSD, Janssen; Consulting: Falk Pharma, Phenex, Amgen; Grant/Research Support: Intercept; Patent Held/Filed: Med Uni Graz (norUDCA); Speaking and Teaching: Falk Foundation, Roche, Gilead The following people have nothing to disclose: Christian Kienbacher, Martin Gajdosik, Michael Krebs, Stefan Traussnigg, Werner Dolak, Petra E.

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