title: Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model.
abstract: We generated mice that overexpress protein targeting to glycogen (PTG) in the liver (PTG(OE)), which results in an increase in liver glycogen. When fed a high-fat diet (HFD), these animals reduced their food intake. The resulting effect was a lower body weight, decreased fat mass, and reduced leptin levels. Furthermore, PTG overexpression reversed the glucose intolerance and hyperinsulinemia caused by the HFD and protected against HFD-induced hepatic steatosis. Of note, when fed an HFD, PTG(OE) mice did not show the decrease in hepatic ATP content observed in control animals and had lower expression of neuropeptide Y and higher expression of proopiomelanocortin in the hypothalamus. Additionally, after an overnight fast, PTG(OE) animals presented high liver glycogen content, lower liver triacylglycerol content, and lower serum concentrations of fatty acids and β-hydroxybutyrate than control mice, regardless of whether they were fed an HFD or a standard diet. In conclusion, liver glycogen accumulation caused a reduced food intake, protected against the deleterious effects of an HFD, and diminished the metabolic impact of fasting. Therefore, we propose that hepatic glycogen content be considered a potential target for the pharmacological manipulation of diabetes and obesity.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain CIBERDEM, Madrid, Spain.
authors.forename: Iliana
authors.initials: I
authors.lastname: López-Soldado
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain CIBERDEM, Madrid, Spain.
authors.forename: Delia
authors.initials: D
authors.lastname: Zafra
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain CIBERDEM, Madrid, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Duran
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Adrover
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain CIBERDEM, Madrid, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Calbó
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain CIBERDEM, Madrid, Spain Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain guinovart@irbbarcelona.org.
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Guinovart
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004435:Eating / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D009765:Obesity / Q000097:blood / Q000378:metabolism* / Q000517:prevention & control
chemical_list: D002352:Carrier Proteins; D020738:Leptin; D008112:Liver Glycogen; D000255:Adenosine Triphosphate