Iliana López-Soldado1,2, Rebeca Fuentes-Romero1, Jordi Duran1,2, Joan J Guinovart3,4,5. 1. Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028, Barcelona, Spain. 2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain. 3. Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri i Reixac 10, 08028, Barcelona, Spain. guinovart@irbbarcelona.org. 4. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain. guinovart@irbbarcelona.org. 5. Department of Biochemistry and Molecular Biomedicine, University of Barcelona, Barcelona, Spain. guinovart@irbbarcelona.org.
Abstract
AIMS/HYPOTHESIS: Liver glycogen plays a key role in regulating food intake and blood glucose. Mice that accumulate large amounts of this polysaccharide in the liver are protected from high-fat diet (HFD)-induced obesity by reduced food intake. Furthermore, these animals show reversal of the glucose intolerance and hyperinsulinaemia caused by the HFD. The aim of this study was to examine the involvement of the hepatic branch of the vagus nerve in regulating food intake and glucose homeostasis in this model. METHODS: We performed hepatic branch vagotomy (HBV) or a sham operation on mice overexpressing protein targeting to glycogen (Ptg OE). Starting 1 week after surgery, mice were fed an HFD for 10 weeks. RESULTS: HBV did not alter liver glycogen or ATP levels, thereby indicating that this procedure does not interfere with hepatic energy balance. However, HBV reversed the effect of glycogen accumulation on food intake. In wild-type mice, HBV led to a significant reduction in body weight without a change in food intake. Consistent with their body weight reduction, these animals had decreased fat deposition, adipocyte size, and insulin and leptin levels, together with increased energy expenditure. Ptg OE mice showed an increase in energy expenditure and glucose oxidation, and these differences were abolished by HBV. Moreover, Ptg OE mice showed an improvement in HFD-induced glucose intolerance, which was suppressed by HBV. CONCLUSIONS/ INTERPRETATION: Our results demonstrate that the regulation of food intake and glucose homeostasis by liver glycogen is dependent on the hepatic branch of the vagus nerve.
AIMS/HYPOTHESIS: Liver glycogen plays a key role in regulating food intake and blood glucose. Mice that accumulate large amounts of this polysaccharide in the liver are protected from high-fat diet (HFD)-induced obesity by reduced food intake. Furthermore, these animals show reversal of the glucose intolerance and hyperinsulinaemia caused by the HFD. The aim of this study was to examine the involvement of the hepatic branch of the vagus nerve in regulating food intake and glucose homeostasis in this model. METHODS: We performed hepatic branch vagotomy (HBV) or a sham operation on mice overexpressing protein targeting to glycogen (Ptg OE). Starting 1 week after surgery, mice were fed an HFD for 10 weeks. RESULTS: HBV did not alter liver glycogen or ATP levels, thereby indicating that this procedure does not interfere with hepatic energy balance. However, HBV reversed the effect of glycogen accumulation on food intake. In wild-type mice, HBV led to a significant reduction in body weight without a change in food intake. Consistent with their body weight reduction, these animals had decreased fat deposition, adipocyte size, and insulin and leptin levels, together with increased energy expenditure. Ptg OEmice showed an increase in energy expenditure and glucose oxidation, and these differences were abolished by HBV. Moreover, Ptg OEmice showed an improvement in HFD-induced glucose intolerance, which was suppressed by HBV. CONCLUSIONS/ INTERPRETATION: Our results demonstrate that the regulation of food intake and glucose homeostasis by liver glycogen is dependent on the hepatic branch of the vagus nerve.
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