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

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

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Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland.



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.


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.


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.


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).


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.

[Indexed for MEDLINE]

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