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

Riyue Bao, Kenneth G. Onishi, Elisabetta Tolla, Fran J. P. Ebling, J E Lewis, R. L. Anderson, Perry Barrett, Brian J. Prendergast, Tyler J. Stevenson (Corresponding Author)

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.
Original languageEnglish
Pages (from-to)13116-13121
Number of pages6
JournalPNAS
Volume116
Issue number26
Early online date12 Jun 2019
DOIs
Publication statusPublished - 25 Jun 2019

Fingerprint

Phodopus
Pro-Opiomelanocortin
Gene Expression Profiling
Hypothalamus
Body Weight Changes
Genome
Physiological Adaptation
Food
Thyroid Hormone Receptors
Diencephalon
Arvicolinae
Photoperiod
Triiodothyronine
Transcriptome
Cricetinae
Computer Simulation
Cues
Dissection
Rodentia
Body Weight

Keywords

  • triiodothyronine
  • proopiomelanocortin
  • seasonal
  • obesity
  • Obesity
  • Proopiomelanocortin
  • Triiodothyronine
  • Seasonal
  • FOOD-INTAKE
  • INFORMATION
  • RECEPTOR
  • IODOTHYRONINE DEIODINASE EXPRESSION
  • PHOTOPERIOD
  • BODY-WEIGHT
  • PROOPIOMELANOCORTIN
  • GENE-EXPRESSION
  • MICE
  • REPRODUCTION

ASJC Scopus subject areas

  • General

Cite this

Bao, R., Onishi, K. G., Tolla, E., Ebling, F. J. P., Lewis, J. E., Anderson, R. L., ... Stevenson, T. J. (2019). Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify novel mechanisms for seasonal energy balance. PNAS, 116(26), 13116-13121. https://doi.org/10.1073/pnas.1902896116

Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify novel mechanisms for seasonal energy balance. / Bao, Riyue; Onishi, Kenneth G.; Tolla, Elisabetta; Ebling, Fran J. P.; Lewis, J E; Anderson, R. L.; Barrett, Perry; Prendergast, Brian J.; Stevenson, Tyler J. (Corresponding Author).

In: PNAS, Vol. 116, No. 26, 25.06.2019, p. 13116-13121.

Research output: Contribution to journalArticle

Bao, R, Onishi, KG, Tolla, E, Ebling, FJP, Lewis, JE, Anderson, RL, Barrett, P, Prendergast, BJ & Stevenson, TJ 2019, 'Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify novel mechanisms for seasonal energy balance' PNAS, vol. 116, no. 26, pp. 13116-13121. https://doi.org/10.1073/pnas.1902896116
Bao, Riyue ; Onishi, Kenneth G. ; Tolla, Elisabetta ; Ebling, Fran J. P. ; Lewis, J E ; Anderson, R. L. ; Barrett, Perry ; Prendergast, Brian J. ; Stevenson, Tyler J. / Genome sequencing and transcriptome analyses of the Siberian hamster hypothalamus identify novel mechanisms for seasonal energy balance. In: PNAS. 2019 ; Vol. 116, No. 26. pp. 13116-13121.
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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.",
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note = "We thank the manuscript reviewers for constructive feedback; David G. Hazlerigg, Cristina Saenz de Miera, and Valerie Simonneaux for genome sequence contributions; Nicolas Scrutton and Lindsey Duguid for expert technical assistance; and Michael Jarsulic for technical assistance on the high-performance computing clusters. 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). The bioinformatics analysis was performed on high-performance computing clusters at the Center for Research Informatics, Biological Sciences Division. P.B. was funded by the Scottish Government Rural and Environment Science and Analytical Services Division grant to the Rowett Institute.",
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AU - Bao, Riyue

AU - Onishi, Kenneth G.

AU - Tolla, Elisabetta

AU - Ebling, Fran J. P.

AU - Lewis, J E

AU - Anderson, R. L.

AU - Barrett, Perry

AU - Prendergast, Brian J.

AU - Stevenson, Tyler J.

N1 - We thank the manuscript reviewers for constructive feedback; David G. Hazlerigg, Cristina Saenz de Miera, and Valerie Simonneaux for genome sequence contributions; Nicolas Scrutton and Lindsey Duguid for expert technical assistance; and Michael Jarsulic for technical assistance on the high-performance computing clusters. 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). The bioinformatics analysis was performed on high-performance computing clusters at the Center for Research Informatics, Biological Sciences Division. P.B. was funded by the Scottish Government Rural and Environment Science and Analytical Services Division grant to the Rowett Institute.

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N2 - 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.

AB - 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.

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KW - obesity

KW - Obesity

KW - Proopiomelanocortin

KW - Triiodothyronine

KW - Seasonal

KW - FOOD-INTAKE

KW - INFORMATION

KW - RECEPTOR

KW - IODOTHYRONINE DEIODINASE EXPRESSION

KW - PHOTOPERIOD

KW - BODY-WEIGHT

KW - PROOPIOMELANOCORTIN

KW - GENE-EXPRESSION

KW - MICE

KW - REPRODUCTION

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