Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease
An elevated intrahepatic triglyceride (IHTG) is the classic feature of nonalcoholic fatty liver disease (NAFLD) and can be reduced by weight loss. It is known that hepatic de novo lipogenesis (DNL) contributes to steatosis in individuals with NAFLD but there is less knowledge about the physiological factors that stimulate hepatic DNL and the effect of weight loss on hepatic DNL. Gordon I. Smith and colleagues conducted a study titled “Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease” published in The Journal of Clinical Investigation. The summary of the study is given below:
Objective:
To determine hepatic DNL.
To determine the relationships between hepatic DNL and IHTG content and essential factors that might be involved in regulating DNL.
To determine the effect of moderate weight loss on hepatic DNL, IHTG content, integrated 24-hour plasma insulin, and glucose concentrations, and liver and whole-body insulin sensitivity.
Method:
The study includes lean individuals, obese individuals with normal IHTG content, or obese with NAFLD. Investigators determined hepatic DNL, both liver and whole-body insulin sensitivity, and 24-hour integrated plasma insulin and glucose concentrations in all individuals. With the help of the deuterated water method corrected for the potential confounding contribution of adipose tissue DNL, investigators assessed hepatic DNL. Hyperinsulinemic euglycemic clamp procedure in conjunction with glucose tracer infusion was used to assess liver and whole-body insulin sensitivity. 6 subjects in the obese-NAFLD group were also evaluated before and after a diet-induced weight reduction of 10%.
Findings:
A larger contribution of DNL to IHTG formation was found in individuals with obesity and NAFLD than in lean individuals. The study found a strong negative correlation between the rate of DNL and both hepatic insulin sensitivity and whole-body whereas a positive correlation was found with integrated 24-hour plasma glucose and insulin concentrations. The decrease in hepatic DNL and IHTG content with moderate (10%) weight loss suggests that a decrease in hepatic DNL is an important mechanism responsible for the weight loss–induced decline in IHTG content. Lastly, the study suggests that in individuals with obesity and NAFLD, increases in daily 24-hour plasma glucose and insulin concentrations are major drivers of increased DNL.
Image Credit: (Joenomias) Menno de Jong from Pixabay