@article{squire_andrews_2003, title={Pancreatic triacylglycerol lipase in a hibernating mammal. I. Novel genomic organization}, volume={16}, ISSN={["1094-8341"]}, DOI={10.1152/physiolgenomics.00167.2002}, abstractNote={Pancreatic triacylglycerol lipase ( PTL) is expressed in novel locations during hibernation in the thirteen-lined ground squirrel ( Spermophilus tridecemlineatus). PTL cDNAs isolated from two of these locations, heart and white adipose tissue (WAT), contain divergent 5′-untranslated regions (5′-UTRs) suggesting alternative promoter usage or the possibility of multiple PTL genes in the ground squirrel genome. In addition, cDNAs isolated from WAT contain tracts of retroviral sequence in their 5′-UTRs. Our examination of PTL genomic clones isolated from a thirteen-lined ground squirrel genomic DNA library, coupled with genomic Southern blot analysis, enabled us to conclude that PTL mRNAs expressed in heart and WAT are the products of the same single-copy gene. The 5′ portion of this gene spans 9.2 kb, is composed of 6 exons, and contains a full-length endogenous retroviral genome with conserved long terminal repeats (LTRs). Alignment of the ground squirrel PTL gene with the mouse, rat, and human PTL genes indicates that this retrovirus inserted into the ground squirrel genome ∼200 bases upstream of the original PTL transcriptional start site. The insertion is a relatively recent event based on largely intact open-reading frames containing minimal frame-shift and nonsense mutations. The high-percentage identity (99.2%) shared between the 5′- and 3′-LTRs of this endogenous retrovirus suggests that the insertion occurred as recently as 300,000 years ago.}, number={1}, journal={PHYSIOLOGICAL GENOMICS}, author={Squire, TL and Andrews, MT}, year={2003}, month={Dec}, pages={119–130} } @article{squire_lowe_bauer_andrews_2003, title={Pancreatic triacylglycerol lipase in a hibernating mammal. II. Cold-adapted function and differential expression}, volume={16}, ISSN={["1094-8341"]}, DOI={10.1152/physiolgenomics.00168.2002}, abstractNote={Thirteen-lined ground squirrels ( Spermophilus tridecemlineatus) exploit the low-temperature activity of pancreatic triacylglycerol lipase (PTL) during hibernation. Lipolytic activity at body temperatures associated with hibernation was examined using recombinant ground squirrel and human PTLs expressed in yeast. Both the human and ground squirrel enzymes displayed high activity at temperatures as low as 0°C and showed Q10values of 1.2–1.5 over a range of 37–7°C. These studies indicate that low-temperature lipolysis is a general property of PTL and does not require protein modifications unique to mammalian cells and/or the hibernating state. Western blots show elevated levels of PTL protein during hibernation in both heart and white adipose tissue (WAT). Significant increases in PTL gene expression are seen in heart, WAT, and testes; but not in pancreas, where PTL mRNA levels are highest. Upregulation of PTL in testes is also accompanied by expression of the PTL-specific cofactor, colipase. The multi-tissue expression of PTL during hibernation supports its role as a key enzyme that shows high activity at low temperatures.}, number={1}, journal={PHYSIOLOGICAL GENOMICS}, author={Squire, TL and Lowe, ME and Bauer, VW and Andrews, MT}, year={2003}, month={Dec}, pages={131–140} } @article{buck_squire_andrews_2002, title={Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal}, volume={8}, ISSN={["1094-8341"]}, DOI={10.1152/physiolgenomics.00076.2001}, abstractNote={Hibernation in mammals requires a metabolic shift away from the oxidation of carbohydrates and toward the combustion of stored fatty acids as the primary source of energy during torpor. A key element involved in this fuel selection is pyruvate dehydrogenase kinase isoenzyme 4 (PDK4). PDK4 inhibits pyruvate dehydrogenase and thus minimizes carbohydrate oxidation by preventing the flow of glycolytic products into the tricarboxylic acid cycle. This paper examines expression of the PDK4 gene during hibernation in heart, skeletal muscle, and white adipose tissue (WAT) of the 13-lined ground squirrel, Spermophilus tridecemlineatus. During hibernation PDK4 mRNA levels increase 5-fold in skeletal muscle and 15-fold in WAT compared with summer-active levels. Similarly, PDK4 protein is increased threefold in heart, fivefold in skeletal muscle, and eightfold in WAT. High levels of serum insulin, likely to have an inhibitory effect on PDK4 gene expression, are seen during fall when PDK4 mRNA levels are low. Coordinate upregulation of PDK4 in three distinct tissues suggests a common signal that regulates PDK4 expression and fuel selection during hibernation.}, number={1}, journal={PHYSIOLOGICAL GENOMICS}, author={Buck, MJ and Squire, TL and Andrews, MT}, year={2002}, month={Feb}, pages={5–13} } @article{bauer_squire_lowe_andrews_2001, title={Expression of a chimeric retroviral-lipase mRNA confers enhanced lipolysis in a hibernating mammal}, volume={281}, number={4}, journal={American Journal of Physiology}, author={Bauer, V. W. and Squire, T. L. and Lowe, M. E. and Andrews, M. T.}, year={2001}, pages={R1186–1192} } @article{brown_chua_liu_andrews_vandenbergh_2000, title={Spontaneous mutation in the db gene results in obesity and diabetes in CD-1 outbred mice}, volume={278}, number={2 pt.2}, journal={American Journal of Physiology}, author={Brown, J. A. and Chua, S. C. and Liu, S. M. and Andrews, M. T. and Vandenbergh, J. G.}, year={2000}, pages={R320–330} } @article{pittman_andrews_setzer_1999, title={A feedback loop coupling 5 S rRNA synthesis to accumulation of a ribosomal protein}, volume={274}, ISSN={["0021-9258"]}, DOI={10.1074/jbc.274.47.33198}, abstractNote={We have shown that elevated expression of ribosomal protein L5 in Xenopus embryos results in the ectopic activation of 5 S rRNA genes that are normally inactive. This transcriptional stimulation mimics the effect of overexpressingtranscription factor IIIA (TFIIIA), the 5 S rRNA gene-specific transcription factor. The results support a model in which a network of nucleic acid-protein interactions involving 5 S rRNA, the 5 S rRNA gene, TFIIIA, and L5 mediates both feedback inhibition of 5 S rRNA synthesis and coupling of 5 S rRNA synthesis to accumulation of a ribosomal protein, L5. We propose that these mechanisms contribute to the homeostatic control of ribosome assembly.}, number={47}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Pittman, RH and Andrews, MT and Setzer, DR}, year={1999}, month={Nov}, pages={33198–33201} } @article{andrews_squire_bowen_rollins_1998, title={Low-temperature carbon utilization is regulated by novel gene activity in the heart of a hibernating mammal}, volume={95}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.95.14.8392}, abstractNote={ Hibernation is a physiological adaptation characterized by dramatic decreases in heart rate, body temperature, and metabolism, resulting in long-term dormancy. Hibernating mammals survive for periods up to 6 mo in the absence of food by minimizing carbohydrate catabolism and using triglyceride stores as their primary source of fuel. The cellular and molecular mechanisms underlying the changes from a state of activity to the hibernating state are poorly understood; however, the selective expression of genes offers one level of control. To address this problem, we used a differential gene expression screen to identify genes that are responsible for the physiological characteristics of hibernation in the heart of the thirteen-lined ground squirrel ( Spermophilus tridecemlineatus ). Here, we report that genes for pancreatic lipase and pyruvate dehydrogenase kinase isozyme 4 are up-regulated in the heart during hibernation. Pancreatic lipase is normally expressed exclusively in the pancreas, but when expressed in the hibernating heart it liberates fatty acids from triglycerides at temperatures as low as 0°C. Pyruvate dehydrogenase kinase isozyme 4 inhibits carbohydrate oxidation and depresses metabolism by preventing the conversion of pyruvate to Ac-CoA. The resulting anaerobic glycolysis and low-temperature lipid catabolism provide evidence that adaptive changes in cardiac physiology are controlled by the differential expression of genes during hibernation. }, number={14}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Andrews, MT and Squire, TL and Bowen, CM and Rollins, MB}, year={1998}, month={Jul}, pages={8392–8397} }