Effect of weight loss on liver free fatty acid uptake and hepatic insulin resistance

J Clin Endocrinol Metab. 2009 Jan;94(1):50-5. doi: 10.1210/jc.2008-1689. Epub 2008 Oct 28.


Objective: Weight loss has been shown to decrease liver fat content and whole-body insulin resistance. The current study was conducted to investigate the simultaneous effects of rapid weight reduction with a very-low-calorie diet on liver glucose and fatty acid metabolism and liver adiposity.

Hypothesis: We hypothesized that liver insulin resistance and free fatty acid uptake would decrease after weight loss and that they are associated with reduction of liver fat content.

Design: Thirty-four healthy obese subjects (body mass index, 33.7 +/- 8.0 kg/m(2)) were studied before and after a very-low-calorie diet for 6 wk. Hepatic glucose uptake and endogenous glucose production were measured with [(18)F]fluorodeoxyglucose during hyperinsulinemic euglycemia and fasting hepatic fatty acid uptake with [(18)F]fluoro-6-thia-heptadecanoic acid and positron emission tomography. Liver volume and fat content were measured using magnetic resonance imaging and spectroscopy.

Results: Subjects lost weight (11.2 +/- 2.9 kg; P < 0.0001). Liver volume decreased by 11% (P < 0.002), which was partly explained by decreased liver fat content (P < 0.0001). Liver free fatty acid uptake was 26% lower after weight loss (P < 0.003) and correlated with the decrement in liver fat content (r = 0.54; P < 0.03). Hepatic glucose uptake during insulin stimulation was unchanged, but the endogenous glucose production decreased by 40% (P < 0.04), and hepatic insulin resistance by 40% (P < 0.05).

Conclusions: The liver responds to a 6-wk period of calorie restriction with a parallel reduction in lipid uptake and storage, accompanied by enhancement of hepatic insulin sensitivity and clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Energy Intake
  • Fatty Acids, Nonesterified / metabolism*
  • Female
  • Glucose / metabolism
  • Humans
  • Insulin Resistance*
  • Liver / metabolism*
  • Male
  • Triglycerides / analysis
  • Weight Loss / physiology*


  • Fatty Acids, Nonesterified
  • Triglycerides
  • Glucose