Cited by 154Adipose Tissue and MetabolismRegulation of Appetite and ObesityPhotoreceptor and optogenetics research

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Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons

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Zhang, Kevin X., D’Souza, Shane, Upton, Brian A., Kernodle, Stace, Vemaraju, Shruti, Nayak, Gowri, Gaitonde, Kevin D., Holt, Amanda L., Linne, Courtney D., Smith, April N., Petts, Nathan T., Batie, Matthew, Mukherjee, Rajib, Tiwari, Durgesh, Buhr, Ethan D., Van Gelder, Russell N., Gross, Christina, Sweeney, Alison, Sanchez-Gurmaches, Joan, Seeley, Randy J., Lang, Richard A.·2020·Nature

DOI 10.1038/s41586-020-2683-0PMC PMC8130195

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Abstract

The opsin family of G-protein-coupled receptors are used as light detectors in animals. Opsin 5 (also known as neuropsin or OPN5) is a highly conserved opsin that is sensitive to visible violet light 1,2. In mice, OPN5 is a known photoreceptor in the retina 3 and skin 4 but is also expressed in the hypothalamic preoptic area (POA)5. Here we describe a light-sensing pathway in which POA neurons that express Opn5 regulate thermogenesis in brown adipose tissue (BAT). We show that Opn5 is expressed in glutamatergic warm-sensing POA neurons that receive synaptic input from several thermoregulatory nuclei. We further show that Opn5 POA neurons project to BAT and decrease its activity under chemogenetic stimulation. Opn5-null mice show overactive BAT, increased body temperature, and exaggerated thermogenesis when cold-challenged. Moreover, violet photostimulation during cold exposure acutely suppresses BAT temperature in wild-type mice but not in Opn5-null mice. Direct measurements of intracellular cAMP ex vivo show that Opn5 POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light-sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis.

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Authors: Zhang, K. X., D’Souza, S., Upton, B. A., Kernodle, S., Vemaraju, S., Nayak, G., Gaitonde, K. D., Holt, A. L., Linne, C. D., Smith, A. N., Petts, N. T., Batie, M., Mukherjee, R., Tiwari, D., Buhr, E. D., Van Gelder, R. N., Gross, C., Sweeney, A., Sanchez-Gurmaches, J., Seeley, R. J., & Lang, R. A.
Affiliations: Cincinnati Children's Hospital Medical Center (US)
University of Michigan (US)
Yale University (US)
University of Washington (US)
Corresponding author: Lang, Richard A.
ORCID: Zhang, Kevin X.
D’Souza, Shane
Upton, Brian A.
Kernodle, Stace
Vemaraju, Shruti
Nayak, Gowri
Gaitonde, Kevin D.
Holt, Amanda L.
Linne, Courtney D.
Smith, April N.
Mukherjee, Rajib
Tiwari, Durgesh
Buhr, Ethan D.
Gross, Christina
Sweeney, Alison
Sanchez-Gurmaches, Joan
Seeley, Randy J.
Lang, Richard A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2020-09-02
Volume: 585
Issue: 7825
Pages: 420-425
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-020-2683-0
PMC: PMC8130195
OpenAlex: W3082268778
Cited by: 154
References: 31
Citations by year: 2026: 25 · 2025: 36 · 2024: 19 · 2023: 23 · 2022: 17 · 2021: 30 · 2020: 4
FWCI: 11.12
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: American Heart Association (18CDA34080527)
National Eye Institute (R01EY027077, R01EY032029, R01EY026921, R01EY027711, P30EY001730)
National Institute of General Medical Sciences (T32GM063483, R01GM124246)
National Institute of Diabetes and Digestive and Kidney Diseases (P30DK089503)
Topics: Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
Keywords: OPN5, violet light, thermogenesis, brown adipose tissue, preoptic area, deep brain photoreceptors, thermoregulation, cAMP signaling, cold exposure, glutamatergic neurons, chemogenetic stimulation
MeSH terms: Cyclic AMP, Animals, Body Temperature, Adipose Tissue, Brown, Cold Temperature, Color, Female, Light, Male, Membrane Proteins, Neurons, Preoptic Area, Thermogenesis, Mice, Opsins

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Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons

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