title: Lack of Melanopsin Is Associated with Extreme Weight Loss in Mice upon Dietary Challenge.
abstract: Metabolic disorders have been established as major risk factors for ocular complications and poor vision. However, little is known about the inverse possibility that ocular disease may cause metabolic dysfunction. To test this hypothesis, we assessed the metabolic consequences of a robust dietary challenge in several mouse models suffering from retinal mutations. To this end, mice null for melanopsin (Opn4-/-), the photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs), were subjected to five weeks of a ketogenic diet. These mice lost significantly more weight than wild-type controls or mice lacking rod and cone photoreceptors (Pde6brd1/rd1). Although ipRGCs are critical for proper circadian entrainment, and circadian misalignment has been implicated in metabolic pathology, we observed no differences in entrainment between Opn4-/- and control mice. Additionally, we observed no differences in any tested metabolic parameter between these mouse strains. Further studies are required to establish the mechanism giving rise to this dramatic phenotype observed in melanopsin-null mice. We conclude that the causality between ocular disease and metabolic disorders merits further investigation due to the popularity of diets that rely on the induction of a ketogenic state. Our study is a first step toward understanding retinal pathology as a potential cause of metabolic dysfunction.
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Didem Göz
authors.initials: DG
authors.lastname: Aytürk
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America; Departamento de Fisiologia, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Castrucci
authors.affiliation: Department of Environmental Sciences, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: David E
authors.initials: DE
authors.lastname: Carr
authors.affiliation: Department of Medicine-Division of Endocrinology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Keller
authors.affiliation: Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Provencio
mesh_terms: D000818:Animals; D001481:Basal Metabolism / Q000528:radiation effects; D001831:Body Temperature / Q000528:radiation effects; D002940:Circadian Rhythm / Q000528:radiation effects; D004032:Diet; D055423:Diet, Ketogenic; D005247:Feeding Behavior / Q000528:radiation effects; D005838:Genotype; D008027:Light; D008297:Male; D008810:Mice, Inbred C57BL; D010641:Phenotype; D017299:Rod Opsins / Q000172:deficiency* / Q000378:metabolism; D013686:Telemetry; D013997:Time Factors; D015431:Weight Loss / Q000528:radiation effects; D000099210:Melanopsin
chemical_list: D017299:Rod Opsins; D000099210:Melanopsin