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Circadian-independent light regulation of mammalian metabolism

Nature Metabolism volume 6, pages 1000–1007 (2024)Cite this article

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Abstract

The daily light–dark cycle is a key zeitgeber (time cue) for entraining an organism’s biological clock, whereby light sensing by retinal photoreceptors, particularly intrinsically photosensitive retinal ganglion cells, stimulates the suprachiasmatic nucleus of the hypothalamus, a central pacemaker that in turn orchestrates the rhythm of peripheral metabolic activities. Non-rhythmic effects of light on metabolism have also been long known, and their transduction mechanisms are only beginning to unfold. Here, we summarize emerging evidence that, in mammals, light exposure or deprivation profoundly affects glucose homeostasis, thermogenesis and other metabolic activities in a clock-independent manner. Such light regulation could involve melanopsin-based, intrinsically photosensitive retinal ganglion cell-initiated brain circuits via the suprachiasmatic nucleus of the hypothalamus and other nuclei, or direct stimulation of opsins expressed in the hypothalamus, adipose tissue, blood vessels and skin to regulate sympathetic tone, lipolysis, glucose uptake, mitochondrial activation, thermogenesis, food intake, blood pressure and melanogenesis. These photic signalling events may coordinate with circadian-based mechanisms to maintain metabolic homeostasis, with dysregulation of this system underlying metabolic diseases caused by aberrant light exposure, such as environmental night light and shift work.

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Fig. 1: Effects of physiological daytime light versus LAN in humans.
Fig. 2: Brain circuits mediating non-circadian effects of light.
Fig. 3: Direct light perception by opsins expressed in peripheral tissues triggers metabolic activities.

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Acknowledgements

We thank N. Li for graphic assistance. We are grateful to colleagues studying light signalling whose works have collectively shaped our understanding of this field. F.R. acknowledges support from the National Natural Science Foundation of China (32122026), the Shenzhen Medical Academy of Research and Translation (B2301008), the Shenzhen Science and Technology Innovation Commission (RCJC20221008092757096) and the Shenzhen Science and Technology Program (ZDSYS20220402111000001). T.X. acknowledges support from the National Natural Science Foundation of China (32121002, 81925009), the National Key Basic Research Program of China (2020YFA0112200), the CAS Project for Young Scientists in Basic Research (YSBR-013), the New Cornerstone Science Foundation, and the Tencent Foundation through the XPLORER PRIZE.

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  1. Shenzhen Key Laboratory of Biomolecular Assembling and Regulation, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China

    Feng Rao

  2. Hefei National Research Center for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Tian Xue

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F.R. and T.X. equally conceived the idea, selected the content and wrote the manuscript.

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Rao, F., Xue, T. Circadian-independent light regulation of mammalian metabolism. Nat Metab 6, 1000–1007 (2024). https://doi.org/10.1038/s42255-024-01051-6

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