In a recent perspective piece published in the journal Nature Metabolism, Chinese researchers discussed evidence from recent studies on the non-rhythmic impact of light deprivation or exposure on metabolic activities such as thermogenesis or glucose homeostasis in a manner that is not dependent on the circadian clock.
Perspective: Circadian-independent light regulation of mammalian metabolism. Image Credit: vetre / Shutterstock
Photoreception
Sunlight is the energy source that powers most ecosystems, with primary producers or autotrophs harvesting the energy from light to produce the biomass that fuels most heterotrophs. Furthermore, while animals do not directly harvest the energy from light, photoreceptors expressing opsins in the chromophores and peripheral tissues help them sense light, which acts as an environmental cue for various biological functions.
Mammalian systems largely depend on the eye, which contains rod and cone opsins, to perceive light. However, observations of light detection in animals that do not have functional rod and cone opsins led to the detection of intrinsically photosensitive retinal ganglion cells (ipRGCs). Through non-visual melanopsin, an evolutionarily conserved and primordial light sensor, ipRGCs modulate processes such as mood regulation and pupillary reflexes.
While ipRGCs are involved in setting the circadian rhythm through the suprachiasmatic nucleus of the hypothalamus, recent studies have shown that ipRGCs are also involved in conveying photic signals to other parts of the brain such as the central amygdala and the supraoptic nucleus. These pathways, independent of the suprachiasmatic nucleus of the hypothalamus, are known to mediate a wide range of non-circadian functions, from brain development to glucose homeostasis.
Light at night
Circadian rhythms depend on 24-hour day and night cycles, and exposure to artificial light at night disrupts various physiological properties, some of which are rhythmic, such as metabolism, thermoregulation, sleep, and locomotion. Evidence from individuals working evening or night shifts shows that light is the predominant environmental factor determining endogenous rhythmic activities.
Although the mediation of photoentrainment by the suprachiasmatic nucleus of the hypothalamus is not entirely understood, existing research indicates that the two potential pathways through which the hypothalamus conveys circadian information to the peripheral tissues are through the secretion of hormones such as melatonin and the autonomic nervous system.
However, while photoentrainment is dependent on rhythmic exposure to light and day cycles, experiments involving exposure to artificial light at night can also be used to understand the effects of light exposure other than those regulated by the circadian clock.
Non-circadian regulation through ipRGCs
Studies using murine models have shown that even in the absence of melatonin, exposure to artificial light at night causes pleiotropic changes in metabolic processes such as the secretion of corticosterone, glucose tolerance, gluconeogenesis, core temperature regulation, food intake, and locomotion. Some of these processes are believed to be mediated through hypothalamic projections to the paraventricular nucleus of the hypothalamus, which is the neuroendocrine center.
Viral tracing studies in rodents have also shown that ipRGCs innervate other regions of the brain, such as the supraoptic nucleus and the preoptic area of the hypothalamus, which mediate brain development and non-rapid eye movement sleep, respectively, through neuroendocrine processes independent of the suprachiasmatic nucleus of the hypothalamus.
Through acute blue light exposure, the supraoptic nucleus is also involved in the inhibition of the sympathetic regulation of brown adipose tissue, a process vital to systemic metabolism and energy expenditure. Consequently, glucose-induced thermogenesis is suppressed, and glucose tolerance is impaired, potentially accounting for the negative association between light exposure at night and diabetes.
ipRGC-independent light perception pathways
Opsins are also found in regions outside the eye, such as non-visual neuropsin, which is expressed in the preoptic area of the hypothalamus. Studies using mouse models have found that neuropsin is sensitive to short-wavelength light and regulates thermogenesis involving brown adipose tissue. These findings also suggest the potential use of phototherapy to treat obesity and other metabolic disorders.
Various other opsins are expressed in peripheral organs and tissues in mice and humans, suggesting that light perception can also occur through peripheral tissues. The skin is a prime example, responding to ultraviolet light through melanogenesis.
Studies on mice have also found adipose tissue capable of photoreception, with panopsin or encephalopsin mediating adaptive thermogenesis in brown adipose tissue and lipolysis in white adipose tissue.
Conclusions
Overall, the article presented a detailed discussion of the impact of exposure to or deprivation of light on various metabolic processes in mammalian systems through non-circadian pathways. These pathways included melanopsin-based pathways involving the suprachiasmatic nucleus of the hypothalamus and those where non-visual opsins expressed in peripheral tissues were directly stimulated to regulate metabolic processes such as thermogenesis, food intake, glucose metabolism, and melanogenesis.
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