Adaptive Thermogenesis in Mice Is Enhanced by Opsin 3-Dependent Adipocyte Light Sensing

Gowri Nayak; Kevin X Zhang; Shruti Vemaraju; Yoshinobu Odaka; Ethan D Buhr; Amanda Holt-Jones; Stace Kernodle; April N Smith; Brian A Upton; Shane D'Souza; Jesse J Zhan; Nicolás Diaz; Minh-Thanh Nguyen; Rajib Mukherjee; Shannon A Gordon; Gang Wu; Robert Schmidt; Xue Mei; Nathan T Petts; Matthew Batie; Sujata Rao; John B Hogenesch; Takahisa Nakamura; Alison Sweeney; Randy J Seeley; Russell N Van Gelder; Joan Sanchez-Gurmaches; Richard A Lang

doi:10.1016/j.celrep.2019.12.043

Adaptive Thermogenesis in Mice Is Enhanced by Opsin 3-Dependent Adipocyte Light Sensing

Cell Rep. 2020 Jan 21;30(3):672-686.e8. doi: 10.1016/j.celrep.2019.12.043.

Authors

Gowri Nayak¹, Kevin X Zhang¹, Shruti Vemaraju¹, Yoshinobu Odaka¹, Ethan D Buhr², Amanda Holt-Jones³, Stace Kernodle⁴, April N Smith¹, Brian A Upton¹, Shane D'Souza¹, Jesse J Zhan¹, Nicolás Diaz², Minh-Thanh Nguyen¹, Rajib Mukherjee⁵, Shannon A Gordon², Gang Wu⁶, Robert Schmidt⁶, Xue Mei¹, Nathan T Petts⁷, Matthew Batie⁷, Sujata Rao⁸, John B Hogenesch⁶, Takahisa Nakamura⁹, Alison Sweeney³, Randy J Seeley⁴, Russell N Van Gelder¹⁰, Joan Sanchez-Gurmaches¹¹, Richard A Lang¹²

Affiliations

¹ Center for Chronobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; The Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
² Department of Ophthalmology, University of Washington Medical School, Seattle, WA 98104, USA.
³ Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁴ Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
⁵ Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁶ Center for Chronobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁷ Division of Clinical Engineering, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
⁸ The Cleveland Clinic, Ophthalmic Research, 9500 Euclid Avenue, OH 44195, USA.
⁹ Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA; Department of Metabolic Bioregulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi 980-8575, Japan.
¹⁰ Department of Ophthalmology, University of Washington Medical School, Seattle, WA 98104, USA; Department of Biological Structure, University of Washington Medical School, Seattle, WA 98104, USA; Department of Pathology, University of Washington Medical School, Seattle, WA 98104, USA.
¹¹ Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Pediatrics, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA.
¹² Center for Chronobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; The Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Ophthalmology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267, USA. Electronic address: richard.lang@cchmc.org.

Abstract

Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, in which photoreceptor signals are processed into virtual images, and the circadian system, in which light entrains a physiological clock. Here we describe a light response pathway in mice that employs encephalopsin (OPN3, a 480 nm, blue-light-responsive opsin) to regulate the function of adipocytes. Germline null and adipocyte-specific conditional null mice show a light- and Opn3-dependent deficit in thermogenesis and become hypothermic upon cold exposure. We show that stimulating mouse adipocytes with blue light enhances the lipolysis response and, in particular, phosphorylation of hormone-sensitive lipase. This response is Opn3 dependent. These data establish a key mechanism in which light-dependent, local regulation of the lipolysis response in white adipocytes regulates energy metabolism.

Keywords: OPN3; adipocyte; encephalopsin; light; lipolysis; metabolism; mitochondria; opsin; thermogenesis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adipocytes, Brown / metabolism*
Adipocytes, Brown / radiation effects*
Adipocytes, White / metabolism*
Adipocytes, White / radiation effects*
Animals
Cold Temperature
Energy Metabolism / radiation effects
Gene Expression Profiling
Light*
Lipolysis / radiation effects
Mice, Inbred C57BL
Phenotype
Photons
Rod Opsins / metabolism*
Thermogenesis / genetics
Thermogenesis / radiation effects*

Substances

OPN3 protein, mouse
Rod Opsins

Abstract

Publication types

MeSH terms

Substances

Grants and funding