Liver glycogen reduces food intake and attenuates obesity in a high-fat diet-fed mouse model

Iliana López-Soldado, Delia Zafra, Jordi Duran, Anna Adrover, Joaquim Calbó, Joan J. Guinovart

Research output: Indexed journal article Articlepeer-review

43 Citations (Scopus)

Abstract

We generated mice that overexpress protein targeting to glycogen (PTG) in the liver (PTGOE), 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, PTGOE 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, PTGOE 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.

Original languageEnglish
Pages (from-to)796-807
Number of pages12
JournalDiabetes
Volume64
Issue number3
DOIs
Publication statusPublished - Mar 2015
Externally publishedYes

Keywords

  • Impaired glucose-tolerance
  • Protein phosphatase-1
  • Rat hepatocytes
  • Hepatic overexpression
  • Glucokinase expression
  • Targeting subunit
  • Lipid-synthesis
  • Synthase
  • Mice
  • Hyperphagia

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