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Effect of Weight Loss on Liver Free Fatty Acid Uptake and Hepatic Insulin Resistance

Turku Positron Emission Tomography (PET) Centre (A.P.M.V., P.I., R.B., M.K., A.K., R.L., M.J., L.G., P.N.), and Departments of Radiology (R.P., P.N.), Medicine (T.R.), and Clinical Physiology (O.T.R.), University of Turku and Turku University Hospital, Turku, Finland; PET Centre (P.I., L.G.), Institute of Clinical Physiology, Consiglio Nazionale delle Ricerche National Research Council, Pisa, Italy; Department of Clinical Chemistry (T.L.), University of Tampere and Tampere University Hospital; and Institute of Biomedical Engineering (A.M.), National Research Council, Padua, Italy

Address all correspondence and requests for reprints to: Dr. Pirjo Nuutila, Turku PET Centre, Turku University Hospital, P.O. Box 52, FIN-20521, Turku, Finland. E-mail: pirjo.nuutila{at}utu.fi.

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/m²) were studied before and after a very-low-calorie diet for 6 wk. Hepatic glucose uptake and endogenous glucose production were measured with [¹⁸F]fluorodeoxyglucose during hyperinsulinemic euglycemia and fasting hepatic fatty acid uptake with [¹⁸F]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.