Subjects with non alcoholic fatty liver disease (NAFLD) display increased visceral and pancreatic fat associated with worse metabolic profile

Together with insulin resistance (IR), lipotoxicity and inflammation, patients with non-alcoholic fatty liver diseases (NAFLD) often show increased visceral fat (VF) that correlates with increased insulin and hepatic fat (HF). If VF is playing a key role in the progression of liver disease is not clear. Beyond VF and HF, fat can also accumulate in the pancreas (PF) leading to impaired insulin secretion and increasing the risk of diabetes (T2DM). The aim of this work was to measure by magnetic resonance (MR) the separate impact of VF, HF and PF on histological liver damage, lipid profile and metabolic alterations in non diabetic patients with biopsy proven NAFLD. Methods: We studied 34 non diabetic subjects with NAFLD (biopsy scored according to Kleiner) and 8 healthy controls (CT). We measured plasma concentrations of triglycerides (TG), free fatty acids (FFA), insulin, C-peptide, monocyte chemoattractant protein-1(MCP-1) and adiponectin, FFAs composition by chromatography mass spectrometry (GCMS), visceral, hepatic and pancreatic fat by MR. In addition, using tracers, we evaluated lipolysis and endogenous glucose production (EGP). We calculated indexes of IR (i.e., HOMA, Adipo-IR =Lipolysis x Insulin and Hep-IR= EGP x Insulin); the ratios palmitic/linoleic acid (16:0/18:2, an indirect index of de novo lipogenesis, DNL) and the saturated to unsaturated fat ratio (SFA/PUFA, associated with impaired lipid metabolism and oxidative stress). Results: NAFLD patients with fibrosis F1-4 (n=24) had a worse metabolic profile compared to NAFLD with F0 (n=10) and CT, showing increased parameters of insulin resistance, inflammation (MCP-1) and lipotoxicity (i.e. increased DNL index and SFA/PUFA). Visceral and hepatic fat were both significantly increased in NAFLD, especially in F1-4 vs F0 vs CT (VF=2.9±1.1 vs 2.1±0.6 kg vs 0.7±0.4 kg p<0.05; HF=0.45±0.05 vs 0.32±0.08 kg vs 0.1±0.1 kg p<0.01 respectively); PF was significantly increased in subjects with F1-4 compared to F0+CT (p=0.3). In the whole group, HF correlated with both VF (r=0.47) and PF (r=0.41). HF and VF correlated positively with high C-peptide and insulin (all r>0.4; all p<0.05), HOMA, Hep-IR and Adipo-IR (all r>0.4; all p<0.05), parameters of lipotoxicity (palmitic/linoleic acid ratio, SFA/PUFA) (all r>0.3; all p<0.05) and inflammation (MCP-1) (all r>0.5; all p<0.01) and inversely associated with adiponectin (all r>0.5; all p<0.001) while PF correlated only with C-peptide (i.e., pre-hepatic insulin secretion). Conclusions: NAFLD patients show increased visceral and pancreatic fat accumulation associated with an adverse metabolic profile but also with higher degree of liver damage.