Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals

Marcus M. Seldin, Mardi S. Byerly, Pia S. Petersen, Roy Swanson, Anne Balkema-Buschmann, Martin H. Groschup, G. William Wong

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Mammalian hibernation elicits profound changes in whole-body physiology. The liver-derived hibernation protein (HP) complex, consisting of HP-20, HP-25 and HP-27, was shown to oscillate circannually, and this oscillation in the central nervous system (CNS) was suggested to play a role in hibernation. The HP complex has been found in hibernating chipmunks but not in related nonhibernating tree squirrels, leading to the suggestion that hibernationspecific genes may underlie the origin of hibernation. Here, we show that non-hibernating mammals express and regulate the conserved homologous HP complex in a seasonal manner, independent of hibernation. Comparative analyses of cow and chipmunk HPs revealed extensive biochemical and structural conservations. These include liver-specific expression, assembly of distinct heteromeric complexes that circulate in the blood and cerebrospinal fluid, and the striking seasonal oscillation of the HP levels in the blood and CNS. Central administration of recombinant HPs affected food intake in mice, without altering body temperature, physical activity levels or energy expenditure. Our results demonstrate that HP complex is not unique to the hibernators and suggest that the HP-regulated liver-brain circuit may couple seasonal changes in the environment to alterations in physiology.

Original languageEnglish (US)
Pages (from-to)2667-2679
Number of pages13
JournalJournal of Experimental Biology
Issue number15
StatePublished - Aug 1 2014


  • CTRP
  • Cerebrospinal fluids
  • Hibernation
  • Metabolism
  • Plasma proteins

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Physiology
  • Aquatic Science
  • Animal Science and Zoology
  • Molecular Biology
  • Insect Science


Dive into the research topics of 'Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals'. Together they form a unique fingerprint.

Cite this