Lack of Melanopsin Is Associated with Extreme Weight Loss in Mice upon Dietary Challenge.
Lack of Melanopsin Is Associated with Extreme Weight Loss in Mice upon Dietary Challenge.
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DOI：
10.1371/journal.pone.0127031
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Provencio I
中科院分区：
文献类型：
--
作者：
Aytürk DG;Castrucci AM;Carr DE;Keller SR;Provencio I
代谢紊乱已被确定为眼部并发症和视力低下的主要危险因素。然而，对于眼部疾病可能导致代谢功能障碍的相反可能性知之甚少。为了验证这一假设，我们在几种患有视网膜突变的小鼠模型中评估了强大的饮食挑战的代谢后果。为此，小鼠黑视素（Opn4-/-）缺失，内在光敏视网膜神经节细胞（ipRGCs）的光色素，进行了五周的生酮饮食。这些小鼠的体重明显比野生型对照或缺乏杆状和锥状光感受器（Pde6brd1/rd1）的小鼠减轻。尽管ipRGCs对于适当的昼夜节律干扰至关重要，并且昼夜节律失调与代谢病理有关，但我们观察到Opn4-/-和对照小鼠在昼夜节律干扰方面没有差异。此外，我们观察到这些小鼠品系之间的任何测试代谢参数均无差异。需要进一步的研究来确定在黑视素缺失的小鼠中观察到的引起这种戏剧性表型的机制。我们的结论是，眼病和代谢紊乱之间的因果关系值得进一步调查，因为依赖于诱导生酮状态的饮食的普及。我们的研究是了解视网膜病理作为代谢功能障碍的潜在原因的第一步。
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.
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DOI：
10.1073/pnas.86.24.9722
发表时间：
1989-12-01
影响因子：
11.1
作者：
BOWES, C;DANCIGER, M;FARBER, DB
通讯作者：
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DOI：
10.1073/pnas.1222150110
发表时间：
2013-07-16
影响因子：
11.1
作者：
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Yau KW
影响因子：
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Schroedl, Falk
影响因子：
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作者：
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