Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons
Open accessAbstract
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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Neuropsin promotes thermogenesis via intrinsically light-sensitive glutamatergic neurons in the preoptic area.
“this opsin promotes thermogenesis via intrinsically light-sensitive glutamatergic neurons in the preoptic area (Zhang et al., 2020).”
From Ventral striatum dopamine release encodes unique properties of visual stimuli in mice (2023) · cites this paper as Zhang et al., 2020
The paper identifies OPN5 (neuropsin) in glutamatergic, light-sensitive preoptic-area neurons, but the claimed direction of its effect is reversed. The Discussion states that OPN5 inhibits brown adipose tissue thermogenesis; the Abstract likewise reports that stimulating these neurons decreases BAT activity. (LLM, conf=0.90)
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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
- Venue
- Nature
- Published
- 2020-09-02
- Volume
- 585
- Issue
- 7825
- Pages
- 420-425
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- 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 › 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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