Cell Reports (Jan 2020)
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
Affiliations
- Gowri Nayak
- 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
- Kevin X. Zhang
- 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
- Shruti Vemaraju
- 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
- Yoshinobu Odaka
- 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
- Ethan D. Buhr
- Department of Ophthalmology, University of Washington Medical School, Seattle, WA 98104, USA
- Amanda Holt-Jones
- Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA
- Stace Kernodle
- Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA
- April N. Smith
- 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
- Brian A. Upton
- 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
- Shane D’Souza
- 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
- Jesse J. Zhan
- 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
- Nicolás Diaz
- Department of Ophthalmology, University of Washington Medical School, Seattle, WA 98104, USA
- Minh-Thanh Nguyen
- 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
- Rajib Mukherjee
- Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Shannon A. Gordon
- Department of Ophthalmology, University of Washington Medical School, Seattle, WA 98104, USA
- Gang Wu
- 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
- Robert Schmidt
- 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
- Xue Mei
- 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
- Nathan T. Petts
- Division of Clinical Engineering, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Matthew Batie
- Division of Clinical Engineering, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
- Sujata Rao
- The Cleveland Clinic, Ophthalmic Research, 9500 Euclid Avenue, OH 44195, USA
- John B. Hogenesch
- 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
- Takahisa Nakamura
- 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
- Alison Sweeney
- Department of Physics and Astronomy, University of Pennsylvania, Philadelphia, PA 19104, USA
- Randy J. Seeley
- Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA
- Russell N. Van Gelder
- 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
- Joan Sanchez-Gurmaches
- 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
- Richard A. Lang
- 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; Corresponding author
- Journal volume & issue
-
Vol. 30,
no. 3
pp. 672 – 686.e8
Abstract
Summary: 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. : White adipocytes activate the lipolysis pathway to produce the free fatty acids that are used as heating fuel by brown adipose tissue. Nayak et al. show that Opsin 3 is required for blue-light-enhanced activation of the lipolysis pathway. This explains the low body temperature of Opn3 mutant mice. Keywords: OPN3, encephalopsin, opsin, light, thermogenesis, adipocyte, lipolysis, metabolism, mitochondria
