Advertisement

Resource and Technical AdvanceIn-Press PreviewGeneticsMetabolism Open Access | 10.1172/jci.insight.149137

Gene expression atlas of energy balance brain regions

Maria Caterina De Rosa,1 Hannah J. Glover,1 George Stratigopoulos,1 Charles A. LeDuc,1 Qi Su,2 Yufeng Shen,3 Mark W. Sleeman,4 Wendy K. Chung,1 Rudolph L. Leibel,1 Judith Y. Altarejos,2 and Claudia A. Doege5

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by De Rosa, M. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Glover, H. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Stratigopoulos, G. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by LeDuc, C. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Su, Q. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Shen, Y. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Sleeman, M. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Chung, W. in: JCI | PubMed | Google Scholar |

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Leibel, R. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Altarejos, J. in: JCI | PubMed | Google Scholar

1Department of Pediatrics, Columbia University, New York, United States of America

2Regeneron Pharmaceuticals Inc, Tarrytown, United States of America

3Department of Systems Biology, Columbia University, New York, United States of America

4Regeneron Pharmaceutical Inc, Tarrytown, United States of America

5Naomi Berrie Diabetes Center, Columbia University, New York, United States of America

Find articles by Doege, C. in: JCI | PubMed | Google Scholar

Published July 20, 2021 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.149137.
Copyright © 2021, De Rosa et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published July 20, 2021 - Version history
View PDF
Abstract

Energy balance is controlled by interconnected brain regions in the hypothalamus, brain stem, cortex and limbic system. Gene expression signatures of these regions can help elucidate the pathophysiology underlying obesity. RNA sequencing was conducted on P56 C57BL/6NTac male mice and E14.5 C57BL/6NTac embryos punch-biopsies in 16 obesity-relevant brain regions. The expression of 190 known obesity-associated genes (monogenic, rare and low-frequency coding variants, genome-wide association studies (GWAS), syndromic) were analyzed in each anatomical region. Genes associated with these genetic categories of obesity had localized expression patterns across brain regions. Known monogenic obesity causal genes were highly enriched in the arcuate nucleus of the hypothalamus and developing hypothalamus. The obesity-associated genes clustered into distinct ‘modules’ of similar expression profile and these are distinct from expression ‘modules’ formed by similar analysis with genes known to be associated with other disease phenotypes (type 1 and type 2 diabetes, autism, breast cancer) in the same energy balance-relevant brain regions.

Graphical Abstract
graphical abstract
Supplemental material

View

View Supplemental Table 6

View Supplemental Table 14

Version history
  • Version 1 (July 20, 2021): In-Press Preview
Advertisement
Advertisement