title: Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals.
abstract: 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 non-hibernating tree squirrels, leading to the suggestion that hibernation-specific 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.
authors: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Marcus M
authors: MM
authors: Seldin
authors: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Mardi S
authors: MS
authors: Byerly
authors: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Pia S
authors: PS
authors: Petersen
authors: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors: Roy
authors: R
authors: Swanson
authors: Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany.
authors: Anne
authors: A
authors: Balkema-Buschmann
authors: Institute for Novel and Emerging Infectious Diseases, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, 17493 Greifswald-Insel Riems, Germany.
authors: Martin H
authors: MH
authors: Groschup
authors: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA gwwong@jhmi.edu.
authors: G William
authors: GW
authors: Wong
mesh_terms: D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000378:metabolism; D001831:Body Temperature; D002417:Cattle / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism* / Q000502:physiology; D004435:Eating / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008124:Locomotion; D051379:Mice / Q000378:metabolism; D046912:Multiprotein Complexes / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000378:metabolism*; D010802:Phylogeny; D012589:Sciuridae / Q000378:metabolism; D012621:Seasons; D016415:Sequence Alignment
chemical_list: D001798:Blood Proteins; D046912:Multiprotein Complexes
keywords: CTRP; Cerebrospinal fluids; Hibernation; Metabolism; Plasma proteins