Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization

Nat Commun. 2013;4:2316. doi: 10.1038/ncomms3316.


During fasting, animals maintain their energy balance by shifting their energy source from carbohydrates to triglycerides. However, the trigger for this switch has not yet been entirely elucidated. Here we show that a selective hepatic vagotomy slows the speed of fat consumption by attenuating sympathetic nerve-mediated lipolysis in adipose tissue. Hepatic glycogen pre-loading by the adenoviral overexpression of glycogen synthase or the transcription factor TFE3 abolished this liver-brain-adipose axis activation. Moreover, the blockade of glycogenolysis [corrected] through the knockdown of the glycogen phosphorylase gene and the resulting elevation in the glycogen content abolished the lipolytic signal from the liver, indicating that glycogen is the key to triggering this neurocircuitry. These results demonstrate that liver glycogen shortage activates a liver-brain-adipose neural axis that has an important role in switching the fuel source from glycogen to triglycerides under prolonged fasting conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / innervation*
  • Adipose Tissue / metabolism
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / biosynthesis
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Brain / metabolism
  • Energy Metabolism
  • Fasting / metabolism*
  • Glycogen Phosphorylase / genetics
  • Glycogen Phosphorylase / metabolism
  • Glycogen Synthase / biosynthesis
  • Glycogen Synthase / genetics
  • Glycogen Synthase / metabolism
  • Glycogenolysis / genetics
  • Guanethidine / pharmacology
  • Lipolysis / physiology
  • Liver / innervation
  • Liver / metabolism
  • Liver Glycogen / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nerve Block
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / metabolism*
  • Sympatholytics / pharmacology
  • Triglycerides / metabolism*
  • Vagus Nerve / surgery


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Liver Glycogen
  • Sympatholytics
  • Triglycerides
  • Tcfe3 protein, mouse
  • Glycogen Phosphorylase
  • Glycogen Synthase
  • Guanethidine