Metabolic handling of an oral fat load in NAFLD patients.

The necro-inflammatory processes in the liver of NAFLD patients may be directly related to the extent of lipid flux, but also to the composition of fatty acids delivered to and stored within the liver. The relative importance of quality vs quantity of fat delivered to the liver in the pathogenesis of NAFLD/NASH is currently unclear. Aims: To investigate the basal and post-load whole body lipolysis and composition of plasma non-esterified free fatty acids (NEFA) in NAFLD subjects. Methods: We performed an oral fat load (200 ml dairy cream and egg yolk) in combination with [2H5]glycerol in 8 non-obese, normolipidaemic, non-diabetic patients with biopsy-proven NAFLD and 4 controls. Plasma lipids were measured by automated enzymatic methods. NEFA composition was assessed by high performance liquid chromatography and reported as percentage. Total post-load area under the curve (AUC) and incremental AUC (IAUC) of lipids were calculated. Whole body lipolysis and Adipose tissue IR index were derived from glycerol Ra. Results: Despite the absence of diabetes, obesity and overt dyslipidaemia, in NAFLD patients post-load triglycerides (TG) and VLDL-TG plasma concentrations were increased at all curve time-points, reaching a maximum after 4 hours. (TG p=0.029 and VLDL-TG p=0,038 vs controls). Similarly, the TG-AUC was increased by 50% (p=0.018) and the IAUC-TG was increased 2-fold (p=0.025). Conversely, post-load ApoB48 and ApoB100 plasma concentrations and their respective AUCs were significantly reduced (p<0.05 for all of them). NAFLD patients had significantly higher concentration of NEFA than controls (P<0.05), higher total saturated and monounsaturated levels (P<0.05), mainly due to the increase of palmitoleic, oleic and stearic acids. Basal glycerol Ra and Adipo_IR were significantly increased (p<0.03 and p<0.001 respectively in NAFLD vs controls) and post-load glycerol Ra was less suppressed (p=0.05), despite higher post-load insulin concentrations. Conclusions: Metabolic handling of an oral fat load in NAFLD patients is characterised by 1. increased triglyceride levels; 2. reduced ApoB48 and ApoB100 levels, compatible with defective intestinal absorption and impaired liver synthesis respectively; 3. a NEFA pattern dominated by saturated and monounsaturated FAs. and 4. increased adipose tissue lipolytic activity both fasting and postprandially. All these alterations may contribute to the progression of liver damage in NAFLD patients.