Contribution of visceral fat and hepatic fat to metabolic derangements and liver damage in NAFLD patients.

Background: Both hepatic (HF) and visceral fat (VF) are involved in the onset and progression of metabolic syndrome and NAFLD. However, their relative role is still debated. Aim: To determine the relative contribution of HF and VF to both metabolic derangements and histological liver damage in NAFLD patients. Methods: In 22 non-diabetic, non-dyslipidaemic patients with biopsy-proven NAFLD we measured whole abdomen VF by MRI, fasting endogenous glucose production (EGP) and lipolysis by tracer infusion, peripheral insulin resistance (IR) as HOMA, Hepatic-IR (EGP*insulin) and Adipo-IR (FFA*Insulin). Hepatic histology was scored according to Kleiner, HF was assessed as percentage of liver fat. Results: VF increased with BMI (r=0.54, p<0.004) and HF (r=0.43, p<0.03), whereas HF was not correlated with BMI. Only HF, but not VF, was associated with circulating FFA levels (r=0.51, p<0.01), and Adipo-IR (r=0.41, p<0.05), while no correlation was found between either LF% or VF with Hepatic-IR or HOMA. Patients with NAS score ≥4 (vs. NAS 0–3) had increased VF (3.9±0.7 vs. 2.8±0.4 kg), FFA concentrations (525±52 vs. 804±98 mmol/l), peripheral IR (HOMA: 3.7±0.5 vs. 2.8±0.8), Hepatic-IR (169±23 vs. 124±32), and Adipo-IR (13.2±2.5 vs. 6.3±1.8) (all p<0.05). Considering only balloning and lobular inflammation in the NAS score, subjects with a composite score >2 had an impaired lipolysis suppression. Patients with fibrosis vs. those without fibrosis, had increased VF (3.9±0.6 vs. 2.7±0.7 kg, p<0.03), but not HF, and no differences were found in the indexes of IR. Conclusions: In NAFLD subjects, hepatic fat is associated with metabolic derangements and IR, but Adipo-IR and visceral fat accumulation appear to provide a major contribution to liver damage.