title: Modulation of Gene Expression in Key Survival Pathways During Daily Torpor in the Gray Mouse Lemur, Microcebus murinus.
abstract: A variety of mammals employ torpor as an energy-saving strategy in environments of marginal or severe stress either on a daily basis during their inactive period or on a seasonal basis during prolonged multi-day hibernation. Recently, a few Madagascar lemur species have been identified as the only primates that exhibit torpor; one of these is the gray mouse lemur (Microcebus murinus). To explore the regulatory mechanisms that underlie daily torpor in a primate, we analyzed the expression of 28 selected genes that represent crucial survival pathways known to be involved in squirrel and bat hibernation. Array-based real-time PCR was used to compare gene expression in control (aroused) versus torpid lemurs in five tissues including the liver, kidney, skeletal muscle, heart, and brown adipose tissue. Significant differences in gene expression during torpor were revealed among genes involved in glycolysis, fatty acid metabolism, antioxidant defense, apoptosis, hypoxia signaling, and protein protection. The results showed upregulation of select genes primarily in liver and brown adipose tissue. For instance, both tissues showed elevated gene expression of peroxisome proliferator activated receptor gamma (ppargc), ferritin (fth1), and protein chaperones during torpor. Overall, the data show that the expression of only a few genes changed during lemur daily torpor, as compared with the broader expression changes reported for hibernation in ground squirrels. These results provide an indication that the alterations in gene expression required for torpor in lemurs are not as extensive as those needed for winter hibernation in squirrel models. However, identification of crucial genes with altered expression that support lemur torpor provides key targets to be explored and manipulated toward a goal of translational applications of inducible torpor as a treatment option in human biomedicine.
authors.affiliation: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Biochemistry Department, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
authors.forename: Kyle K
authors.initials: KK
authors.lastname: Biggar
authors.affiliation: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Department of Biology, Genetics Institute, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Wu
authors.affiliation: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Department of Surgery & Center for Engineering in Medicine, Massachusetts General Hospital & Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Shannon N
authors.initials: SN
authors.lastname: Tessier
authors.affiliation: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada; Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON K7K 7B4, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, 91800 Brunoy, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Pifferi
authors.affiliation: UMR 7179 Centre National de la Recherche Scientifique, Muséum National d'Histoire Naturelle, 91800 Brunoy, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Perret
authors.affiliation: Institute of Biochemistry & Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada. Electronic address: kenneth_storey@carleton.ca.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Storey
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D016565:Cheirogaleidae / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D005786:Gene Expression Regulation; D006605:Hibernation / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012621:Seasons; D064348:Torpor
chemical_list: D012313:RNA
keywords: Chaperone proteins; Daily torpor; Ferritin; PPAR gamma coactivator; Primate hypometabolism