Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease

Abstract

The role of adipose tissue insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear. To evaluate this, we measured in 207 patients with NAFLD (age = 51 ± 1, body mass index = 34.1 ± 0.3 kg/m2) and 22 controls without NAFLD (no NAFLD) adipose tissue insulin resistance by means of a validated index (Adipo‐IRi = plasma free fatty acids [FFA] x insulin [FPI] concentration) and as the suppression of plasma FFA during an oral glucose tolerance test and by a low‐dose insulin infusion. We also explored the relationship between adipose tissue insulin resistance with metabolic and histological parameters by dividing them based on quartiles of adipose tissue insulin resistance (Adipo‐IRi quartiles: Q1 = more sensitive; Q4 = more insulin resistant). Hepatic insulin resistance, measured as an index derived from endogenous glucose production x FPI (HIRi), and muscle insulin sensitivity, were assessed during a euglycemic insulin clamp with 3‐[3H] glucose. Liver fat was measured by magnetic resonance imaging and spectroscopy, and a liver biopsy was performed to assess liver histology. Compared to patients without steatosis, patients with NAFLD were insulin resistant at the level of adipose tissue, liver, and skeletal muscle and had higher plasma aspartate aminotransferase and alanine aminotransferase, triglycerides, and lower high‐density lipoprotein cholesterol and adiponectin levels (all P < 0.01). Metabolic parameters, hepatic insulin resistance, and liver fibrosis (but not necroinflammation) deteriorated as quartiles of adipose tissue insulin resistance worsened (all P < 0.01). Conclusion: Adipose tissue insulin resistance plays a key role in the development of metabolic and histological abnormalities of obese patients with NAFLD. Treatment strategies targeting adipose tissue insulin resistance (e.g., weight loss and thiazolidinediones) may be of value in this population. (HEPATOLOGY 2012)

Levels of circulating adipokines and their relation with glycemic control and insulin resistance in Saudi patients with non-alcoholic fatty liver disease

“…It is believed that IR is related to adipose tissue plays a key role in the development of NAFLD (18). Our study underscores that NAFLD is associated with IR and adipokines alterations.…”

Hepatic iron concentration correlates with insulin sensitivity in nonalcoholic fatty liver disease

“…We found that HIC negatively correlated with six surrogates of insulin resistance relating to different sites of insulin action. These were adipose tissue insulin resistance (Adipo‐IR),24 percentage hepatic steatosis, serum insulin, serum glucose, homeostatic model assessment of insulin resistance (HOMA‐IR),25 and HbA1C (Table 4; Fig. 2B‐E).…”

Ectopic lipid storage in non-alcoholic fatty liver disease is not mediated by impaired mitochondrial oxidative capacity in skeletal muscle

“…Insulin resistance in adipose tissue results in a reduced ability of insulin to suppress fatty acid release from adipose tissue (leading to increased free fatty acid flux to the liver) and the magnitude of adipose insulin resistance is inversely correlated with liver fat [38,39]. Furthermore, characteristics of subcutaneous fat and defective regulation of lipid storage genes in subcutaneous adipose tissue may limit its expandability [40].…”