Adiponectin isoforms, insulin resistance and liver histology in nonalcoholic fatty liver disease

Background: Nonalcoholic fatty liver disease is associated with insulin resistance and low adiponectin levels. Adiponectin circulates as high-, medium- and low-molecular weight complexes, possibly exerting different insulin-sensitising effects. Aim: We investigated adiponectin isoforms in nonalcoholic fatty liver disease in relation to liver disease severity and insulin resistance. Patients and methods: Total adiponectin and isoform distribution were measured in 54 biopsy-proven, non-diabetic nonalcoholic fatty liver disease subjects, divided according to their fasting and 120-min glucose levels during an oral glucose tolerance test, as well as in 44 matched healthy controls. Insulin resistance/sensitivity was estimated in nonalcoholic fatty liver disease by the homeostasis model assessment and the oral glucose insulin sensitivity during oral glucose tolerance test. Total adiponectin and adiponectin isoforms were determined by in-house assays. Results: Total adiponectin was reduced in nonalcoholic fatty liver disease (5.32±1.85 mg/L vs. 9.11±3.46 mg/L), with a relative abundance of high-molecular weight (34% vs. 47%) and low-molecular weight adiponectin (16% vs. 19%), coupled with dearth of medium-molecular weight adiponectin (50% vs. 34%) (P < 0.001 for all comparisons). In nonalcoholic fatty liver disease, adiponectin did not differ in relation to homeostasis model assessment, but levels were remarkably higher in relation to oral glucose insulin sensitivity-determined insulin sensitivity. However, the distribution of isoforms did not vary with disease severity, BMI class, glucose regulation or insulin resistance. Conclusion: Adiponectin levels are reduced in nonalcoholic fatty liver disease, without any significant contribution of isoform distribution to progressive liver disease.