Intrahepatic diacylglycerol content is associated with hepatic insulin resistance in obese subjects

Abstract

Data from studies in animal models indicate that certain lipid metabolites, particularly diacylglycerol, ceramide, and acylcarnitine, disrupt insulin action. We evaluated the relationship between the presence of these metabolites in the liver (assessed by mass spectrometry) and hepatic insulin sensitivity (assessed using a hyperinsulinemic-euglycemic clamp with stable isotope tracer infusion) in 16 obese adults (body mass index, 48 ± 9 kg/m²). There was a negative correlation between insulin-mediated suppression of hepatic glucose production and intrahepatic diacylglycerol (r = -0.609; P = .012), but not with intrahepatic ceramide or acylcarnitine. These data indicate that intrahepatic diacylglycerol is an important mediator of hepatic insulin resistance in obese people with nonalcoholic fatty liver disease.

Figure 1

Relationship between hepatic insulin sensitivity, determined as insulin-mediated suppression of glucose Ra into plasma, and intrahepatic DAG (top), ceramide (middle), and acylcarnitine (bottom) contents. Open symbols represent subjects with no histologic evidence of steatosis. Data for DAG, acylcarnitines, and insulin-mediated suppression of glucose Ra are ranked (n = 16). Data for ceramides are from 15 subjects. Relationships were the same when individual species of DAG, ceramides, and acylcarnitines were analyzed separately.

Figure 2

Relationship between intrahepatic DAG content and hepatic steatosis (top) and the NAFLD activity score (bottom). Open symbols represent subjects with no histologic evidence of steatosis. Data are ranked (n = 16).