no NASH. Both groups were well matched for clinical parameters (e.g. BMI, liver fat, and insulin resistance). Again, no differences were observed in LDL particle size or phenotype or in any lipoprotein subfraction. Conclusion: Patients with NAFLD have a more atherogenic lipo-protein profile (smaller LDL particles and more atherogenic HDL
subparticles) than patients without NAFLD, even when well-matched for BMI and other clinical parameters. We speculate that this lipoprotein profile is driven mostly by buy GSK126 liver fat content and insulin resistance, and appears not to be affected by the severity of liver disease (NASH) or other metabolic features that coexist with NAFLD, such as obesity or hyperglycemia. Disclosures: John Sninsky – Employment: Quest Diagnostics Robert H. Superko – Employment: Celera-Quest Diagnostics Beverly Orsak – Employment: UTHSCSA Kenneth Cusi – Consulting: Merck, Daichi-Sankyo, Roche, Janssen; Grant/ Research Support: Takeda, Novartis, Mannkind The following people have nothing to disclose: Fernando Bril, Arthur M. Baca, Paola Portillo Sanchez, Margaret C. Lo Background and Aim: Although nonalcoholic steatohepati-tis (NASH) is a common liver disease with a risk of progression to cirrhosis, the major cause of morbidity and mortality in NASH is cardiovascular disease (CVD). Oxidative stress and inflammation play a central role in disease progression within the liver but are also independent
predictors of CVD in NASH. Patients with NASH have reduced levels of high density lipoprotein (HDL), which has cardioprotective effects that include HDL dependent reverse cholesterol transport Selleck Pexidartinib (RCT), anti-oxidant and, anti-inflammatory functions. Since insulin resistance, inflammation and oxidative
stress cause HDL dysfunction through alterations of HDL composition, in addition to being medchemexpress key components of NASH pathogenesis, we hypothesized that dyslipidemia-induced hepatic oxidative stress and inflammation in NASH causes loss of RCT and the anti-oxida-tive functions. Methods. HDL functionality was measured using the macrophage cholesterol efflux assay (%) and paraoxonase (PON1) activity (arbitrary units of anti-oxidative function) by a fluorometric assay in apoB-depleted serum from NASH (n=10) and control (n=11) subjects. ATP binding casette subfamily A1 (ABCA1, a protein that transports cholesterol to apoAI forming nascent HDL)-dependent cholesterol efflux was measured in response to induction using 8-Br-cAMP to distinguish ABCA1-dependent and total cholesterol efflux. The ABCA1-de-pendent cholesterol efflux was calculated by substraction of ABCA1-independent from total efflux. Results. NASH patients had higher BMI, HOMA-IR scores, plasma AST, ALT and tri-glycerides while plasma HDLc was non-significanlty lower than controls. However, HDL function quantified by both total and ABCA1-dependent cholesterol efflux capacity of apoB-de-pleted serum from patients with NASH were significantly lower than controls (Total: 15.0±2.4 vs. 19.2.0±2.