April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Loss of Melanopsin Affects the Weight Loss Profile of Mice on a Ketogenic Diet
Author Affiliations & Notes
  • D. Goz
    Department of Biology and Center for Biological Timing, University of Virginia, Charlottesville, Virginia
  • A. M. Castrucci
    Department of Biology and Center for Biological Timing, University of Virginia, Charlottesville, Virginia
    Departamento de Fisiologia, Universidade de São Paulo, São Paulo, Brazil
  • I. Provencio
    Department of Biology and Center for Biological Timing, University of Virginia, Charlottesville, Virginia
  • Footnotes
    Commercial Relationships  D. Goz, None; A.M. Castrucci, None; I. Provencio, None.
  • Footnotes
    Support  NIH grant R01 NS052112
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 676. doi:
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      D. Goz, A. M. Castrucci, I. Provencio; Loss of Melanopsin Affects the Weight Loss Profile of Mice on a Ketogenic Diet. Invest. Ophthalmol. Vis. Sci. 2010;51(13):676.

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Abstract

Purpose: : A small set of retinal ganglion cells (RGCs) in mammals express the photopigment melanopsin, which renders them photosensitive. Melanopsin cells, functioning as both photoreceptors and conduits of light input from rods/cones, provide light information to non-visual centers of the mouse brain, consequently modulating behavioral and physiological rhythms. ipRGCs also project to various brain areas, of which the functions are mostly unknown. Furthermore, light exerts wavelength dependent, acute physiological effects in humans, such as an increase of core body temperature and heart rate, as well as enhanced alertness. The mechanism through which light functions has not been identified. We tested the hypothesis that loss of melanopsin might influence the ability of mice to balance their energy metabolism, and result in an aberrant response to a dietary challenge.

Methods: : We used adult male C57/BL6J mice or melanopsin-null mice (Opn4-/-) congenic on a C57/BL6J background. Both groups were subjected to a ketogenic (very low-carbohydrate) diet under a blue or red 12:12 light-dark (LD) cycle, as well as constant darkness, and their weights were closely monitored. Locomotor activity and body temperature were also recorded under similar conditions to test for circadian entrainment.

Results: : Under a ketogenic diet, C57/BL6J mice experienced weight loss, and then stabilized at around 3 weeks at a slightly lower weight than their initial weight. Opn4-/- mice on a ketogenic diet, on the other hand, continued losing weight until the experiment was terminated at the end of 5 weeks, at which time they had lost more weight than the controls. Mice exposed to red LD cycle encountered a larger weight loss than the blue LD exposed ones on the same diet, in all genotypes. Both blue and red LD cycles used were bright enough to entrain the C57/BL6J mice. No difference was observed in body temperature rhythms of mice under blue and red LD. The difference in weight loss observed among the genotypes appears to be light dependent.

Conclusions: : Photoreception by the melanopsin photopigment affects the metabolic state of mice and seems to protect them against drastic weight loss on a ketogenic diet.

Keywords: ganglion cells • circadian rhythms • metabolism 
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