Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify mechanisms for seasonal energy balance

Bao, R., Onishi, K. G., Tolla, E., Ebling, F. J.P., Lewis, J. E., Anderson, R. L., Barrett, P., Prendergast, B. J. and Stevenson, T. J. (2019) Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify mechanisms for seasonal energy balance. Proceedings of the National Academy of Sciences of the United States of America, 116(26), pp. 13116-13121. (doi: 10.1073/pnas.1902896116) (PMID:31189592) (PMCID:PMC6600942)

Abstract

Synthesis of triiodothyronine (T3) in the hypothalamus induces marked seasonal neuromorphology changes across taxa. How species-specific responses to T3 signaling in the CNS drive annual changes in body weight and energy balance remains uncharacterized. These experiments sequenced and annotated the Siberian hamster (Phodopus sungorus) genome, a model organism for seasonal physiology research, to facilitate the dissection of T3-dependent molecular mechanisms that govern predictable, robust, and long-term changes in body weight. Examination of the Phodopus genome, in combination with transcriptome sequencing of the hamster diencephalon under winter and summer conditions, and in vivo-targeted expression analyses confirmed that proopiomelanocortin (pomc) is a primary genomic target for the long-term T3-dependent regulation of body weight. Further in silico analyses of pomc promoter sequences revealed that thyroid hormone receptor 1β-binding motif insertions have evolved in several genera of the Cricetidae family of rodents. Finally, experimental manipulation of food availability confirmed that hypothalamic pomc mRNA expression is dependent on longer-term photoperiod cues and is unresponsive to acute, short-term food availability. These observations suggest that species-specific responses to hypothalamic T3, driven in part by the receptor-binding motif insertions in some cricetid genomes, contribute critically to the long-term regulation of energy balance and the underlying physiological and behavioral adaptations associated with the seasonal organization of behavior.

• Item Type: Articles
• Additional Information: This project was supported by a project research grant from The British Society for Neuroendocrinology (to T.J.S.); Grants BB/M021629/1 and BB/M001555/1 (to F.J.P.E.) from the Biotechnology and Biological Sciences Research Council, and Grants UL1-TR000430 (to T.J.S. and B.J.P.) and R01-AI067406 (to B.J.P.) from the National Institutes of Health. T.J.S. is funded by The Leverhulme Trust. The Center for Research Informatics was supported by the Biological Sciences Division at the University of Chicago with additional support provided by the Institute for Translational Medicine/Clinical and Translational award (NIH 5UL1TR002389-02) and the University of Chicago Comprehensive Cancer Center Support Grant (NIH Grant P30CA014599).
• Keywords: Obesity, proopiomelanocortin, seasonal, triiodothyronine.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Tolla, Elisabetta and Stevenson, Professor Tyler
• Authors: Bao, R., Onishi, K. G., Tolla, E., Ebling, F. J.P., Lewis, J. E., Anderson, R. L., Barrett, P., Prendergast, B. J., and Stevenson, T. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490
• Published Online: 12 June 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Proceedings of the National Academy of Sciences of the United States of America 116(26): 13116-13121
• Publisher Policy: Reproduced under a Creative Commons License