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Lack of Melanopsin Is Associated with Extreme Weight Loss in Mice upon Dietary Challenge
Didem Göz Aytürk1, Ana Maria Castrucci2, David E Carr3
1Department of Biology, University of Virginia, Charlottesville, Virginia, United States of America.
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.
Insights
Mice lacking melanopsin (Opn4-/-) showed significant weight loss on a ketogenic diet, suggesting ocular disease may impact metabolic function. Further research is needed to understand this link between retinal mutations and metabolic disorders.
Area of Science:
- Ophthalmology
- Metabolic Science
- Neuroscience
Background:
- Metabolic disorders are known risk factors for ocular complications.
- The inverse relationship, where ocular disease may cause metabolic dysfunction, is less understood.
- Intrinsically photosensitive retinal ganglion cells (ipRGCs) play a role in circadian entrainment, which is linked to metabolic health.
Purpose of the Study:
- To investigate if retinal mutations can lead to metabolic dysfunction.
- To assess the metabolic consequences of a ketogenic diet in mice with specific retinal mutations.
- To explore the role of melanopsin-expressing ipRGCs in diet-induced metabolic changes.
Main Methods:
- Utilized mouse models with retinal mutations, including melanopsin-null (Opn4-/-) and rod/cone photoreceptor-deficient (Pde6brd1/rd1) mice.
- Administered a ketogenic diet for five weeks.
- Monitored weight changes and assessed circadian entrainment and other metabolic parameters.
Main Results:
- Melanopsin-null mice exhibited significantly greater weight loss compared to wild-type controls and Pde6brd1/rd1 mice.
- No significant differences in circadian entrainment were observed between Opn4-/- and control mice.
- No differences in other tested metabolic parameters were found among the mouse strains.
Conclusions:
- Ocular pathology, specifically the absence of melanopsin, may contribute to metabolic dysfunction, evidenced by pronounced weight loss on a ketogenic diet.
- The mechanism behind this observed weight loss in melanopsin-null mice requires further investigation.
- This study highlights the need to explore the causality between ocular disease and metabolic disorders, particularly given the prevalence of ketogenic diets.
