Artificial light affects glucose metabolism

By Dr. Liji Thomas, MDReviewed by Benedette Cuffari, M.Sc.Jan 24 2023

Over the past few decades, it has become clear that artificial light contributes to a host of metabolic disorders. However, the link between metabolism and the neurological recognition of light is not well understood.

A recent paper published in the journal Cell assesses the hypothalamus as a possible mediator of the effect of light on metabolism through connections between the retina, brain, and fatty tissue in the body.

Study: Light modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis. Image Credit: Only_NewPhoto / Shutterstock.com

Introduction

Light is ubiquitous and essential in its effect on living organisms on earth. Mammalian light perception acts through retinal light receptors, or photoreceptors, namely, rods and cones.

Light also acts on intrinsically photosensitive retinal ganglion cells (ipRGCs) that express melanopsin, which is a photopigment found within the eyes that is involved in the circadian rhythm, with little to no involvement in sight. These cells project to many areas of the brain, including the olivary pretectal nuclei and suprachiasmatic nucleus (SCN).

These areas of the brain, in turn, control the pupillary light reflex (PLR), the body’s circadian rhythms, sleep and mood, and cognitive functions. This broad range of functionality indicates that these neurological structures also regulate glucose metabolism.

Glucose is the primary fuel for the brain and muscles and, as a result, is crucial to human survival. These organs cannot perform optimally unless glucose is made available at the right time and in the appropriate concentrations.

Previous studies have reported the adverse effect of artificial light on the risk of diabetes and obesity, both of which are metabolic in origin and closely linked to each other. Furthermore, weeks of abnormal light exposure at night dysregulates circadian rhythms, thereby altering glucose metabolism.

The current study corroborates with previous reports that glucose metabolism shifts with circadian rhythms in relation to light intensity and implicates the hypothalamus supraoptic nucleus (SON) in this alteration.

Increased glucose tolerance after exposure to light

The scientists in this study found that mice exhibited higher glucose tolerance (GT) in the dark as compared to those exposed to artificial light. However, both groups of mice had similar insulin sensitivities and baseline blood glucose levels.

The same effect was observed when mice were exposed to both natural sunlight and blue light, with reduced GT compared to either dark conditions or red light.

Spectral power distribution refers (SPD) to a wavelength function that reflects the amount of optical radiation, or power, present at each wavelength in the visible spectrum. In the current study, the researchers measured the SPD of natural sunlight, blue light, dark conditions, and red light as it relates to the activity of mouse melanopsin.

These SPD light values were used to determine the ability of the different light sources to activate ipRGCs. To this end, the light from all sources was converted to equivalent light intensities at 480 nanometers (nm).

Despite original similar photon numbers with blue light, red light, and natural sunlight, the number of photons at 480 nm was reduced by two to three orders of magnitude for red light as compared to blue light or sunlight. Thus, white light, sunlight, and blue light were all able to activate ipRGCs, which indicates the regulatory activity of light on GT through these receptors.

Further studies on knockout mice lacking ipRGC photoreception demonstrated that light did not impact GT levels, which was comparable to wild-type mice that exhibited reduced GT levels in light as compared to when exposed to dark conditions. These findings indicate that ipRGCs are primarily responsible for the effect of light on GT levels and that this effect is not impacted by the circadian phases, thus leading the authors to investigate neural mechanisms that may be responsible for the effect of light on GT levels.

The central role of the SCN

Among the different nuclei within the hypothalamus that receive signal inputs from ipRGCs include the SCN and SON. In fact, the authors of the current study report that about 83% of ipRCGs directly project to the SON.

Altered SCN activity in mice was found to eliminate circadian rhythms; however, lesions in this area did not have an impact on light-mediated reduction in GT. Comparatively, SON lesion inhibited light-induced differences in GT without altering the circadian rhythm. Thus, SON appears to have a more significant role in the effect of light on GT as compared to SCN.

The ipRGC-SON pathway is activated by light to further activate neurons in the paraventricular nucleus (PVN). These neurons release oxytocin and brain-derived neurotrophic factor (BDNF), while PVN neurons also project to neurons in the solitary tract nucleus (NTS) that release the inhibitory peptide GABA.

These GABA-ergic neurons innervate a region that regulates the ability of brown adipose tissue (BAT) to clear and store glucose from the blood. Thus, light regulates GT through the ipRGC-SON-PVN-NTS pathway that ends in this region. Here, sympathetic nerve cells directly boost BAT heat production, which is strongly linked to glucose clearance from the blood.

The outcome of SON activation by light is the inhibition of BAT heat production in response to changing situations. This is mediated by the adrenergic system, specifically the β3 receptors, the effect of which is reduced GT.

This has been confirmed by the reduction in glucose metabolism observed in humans when exposed to light, a process in which BAT-specific heat generation is known to be involved under certain conditions.

What are the conclusions?

The results of the current study indicate that an acute reduction in GT is independent of circadian rhythms and arises through the SON in the hypothalamus. The mechanism does not appear to be neuroendocrine but rather the result of direct neural pathways. This acute effect is on BAT activity, which is mediated by sympathetic signaling.

The circadian-independent nature of the reduction in GT with light exposure could bode poorly for the effect of dining at night on glucose metabolism, especially because GT is already lower at night as compared to during the day. Therefore, the potentially mitigating effect of proper ambient lighting as a public health measure should be studied in such conditions.

The observed effect on GT is highest for blue light.

In the post-industrial era, exposure to excessive artificial lighting seriously perturbs metabolic homeostasis. Our findings in mice and humans provide one possible explanation and may reveal a potential prevention and treatment strategy for metabolic disorders.”