You probably already know that ambient light regulates circadian rhythms by acting on light-sensitive cells in the eye. In case not though, in full white light (which actually contains all colors of light), the rays of the blue and green light spectrum activate melanopsin, a photosensitive protein in specialized cells in the retinae. When light hits these cells, a signal transmits information to the brain’s master clock. By monitoring light exposure, the brain can keep track of what time of day it is. I spoke with Professor Jamie Zeitzer about this on a previous show. We also know that sunlight can stimulate the production of vitamin D and nitric oxide, both of which have important effects on health. New research suggests that sunlight might have previously unrecognized effects on health. Specifically, there may be a link between sunlight and fat metabolism.
Sunlight and Fat Metabolism: Early Clues
It has been known for several decades that a small percentage of blue light can penetrate human skin, and can even reach white subcutaneous adipose tissue. But the relevance of this finding was not obvious. Curiously, it has also been reported that high OPN4 (the gene that encodes the photopigment melanopsin) mRNA levels are found in human subcutaneous fat. Weird… what the heck are light-sensitive eye proteins doing in our fat tissue? Additionally, we now know that fat cells contain transient receptor potential cation (TRPC) channels – membranes in the retinae that open in response to varying intensities of light.
So, blue light can get to subcutaneous fat tissue, and fat cells seem to have the machinery needed to respond to the signal that is transmitted by light. This is very interesting and raises the possibility that visible light penetrates the skin and has effects by activating a melanopsin / TRPC channel signaling pathway in human fat. If such a pathway exists, what would be its functions? Could exposure to visible light influence the regulation of body fat? My guest (inadvertently) found the answers to these fascinating questions.
In this episode of humanOS Radio, I talk to Dr. Peter Light. Dr. Light is a pharmacologist and a leader in the field of cellular electrical activity. He is chief investigator at the Light Lab at the University of Alberta and is Director of the University of Alberta’s Diabetes Institute. His research has focused on islet signaling and diabetes, as well as developing therapies to treat diabetes and other metabolic diseases. Despite his surname, light is actually not his primary field, although this study does make it seem like a fine example of nominative determinism.
Sunlight and Fat Metabolism: A Serendipitous Discovery
One thing I love about this study is that it started as an accident – like many great scientific discoveries throughout history. The research team was trying to engineer white adipocytes that could produce insulin in response to light as a possible therapy for diabetes when they noticed a white-light induced reaction in some cultured human tissue cells. Since there was little relevant information in the scientific literature, they designed some experiments to figure out what was going on.
First, they needed to confirm that fat tissue can respond to light and has the machinery to do so: Here’s what they did:
- They exposed fat cells to a range of different light wavelengths, finding that fat cells were maximally responsive to blue light (light at 450-480nm).
- They tested whether subcutaneous fat tissue expresses melanopsin and TRPC channels, the same machinery that eyes use to respond to light.
Sure enough, their experiments revealed that fat tissue does express these proteins and does respond to light… Whoa!
Sunlight and Fat Metabolism: Implications for Fat Loss and Metabolic Disease?
They then exposed the fat cells to blue light for 4 hours a day for 13 days to see how it affected the structure and function of the adipocytes. Here is what they found:
- After 13 days of light exposure, fat cells were smaller, and there were fewer cells retaining lipid droplets – in other words, they weren’t storing as much fat. This is a big deal, because smaller fat cells are better able to accommodate excess lipid, are less inflammatory, and, generally, are associated with better metabolic health.
- This diminished adipocyte lipid content also resulted in less secretion of adiponectin and leptin. These adipokines are important signaling proteins, but high levels are associated with inflammation and metabolic disease. The researchers also found increased release of glycerol from the fat cells, which suggests a higher rate of lipolysis (fat breakdown).
Overall, these findings suggest that ambient blue light exposure might be an important regulator of fat cell function and metabolic health.
Sunlight and Fat Metabolism: How Can We Take Advantage of These Findings?
This is fairly new territory. It is not entirely clear yet what intensity or duration of light is required to activate this melanopsin / TRPC signaling pathway in living subjects, so it’s tough to make precise light exposure “prescriptions.” Hopefully more research in the future with human participants will resolve some of these lingering questions.
One thing I will note is only very tiny percentages of blue wavelengths seem to penetrate the skin and affect adipose tissue. This means that you need a very bright light source (like sunlight) to activate the pathway. Typical indoor light probably isn’t going to cut it. One more reason that exposure to bright light early in your day is a good idea. (For more on this, check out Greg’s courses on the circadian system. If you haven’t yet signed up for Pro access, you can find them here.)
In the meantime, this study raises exciting questions. Could repeated exposure to blue light serve as a protective mechanism against insulin resistance, chronic systemic inflammation, or even obesity?
Listen to the interview below to learn more!
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Peter Light - 00:05: I think we may have come across a potential mechanism, which feeds into that concept that we may have evolved to have a mechanism, which cells regulate fat storage at different times of the year.
Kendall Kendrick - 00:24: humanOS. Learn. Master. Achieve.
Dan Pardi - 00:36: Dr. Peter Light, Chief Investigator of the Light lab at the University of Alberta's Diabetes Institute, welcome to humanOS Radio.
Peter Light - 00:43: Hello. Good morning.
Dan Pardi - 00:44: Thank you so much for joining us. You've recently published a extraordinarily interesting study showing that there is these light receptors in fat tissue and it's taken the world by storm for people that care about this subject. I really look forward to talking to you about it today but before we begin, please tell us a little bit about yourself and your lab and what you study.
Peter Light - 01:05: Yes, so you can probably tell from my accent I'm originally from the UK just south of London. I did my PhD at University of Birmingham in the Midlands there and came to Canada for a post-doc in 1991 and never really went back. I enjoy Canada, ended up in Alberta, originally in Calgary, then I moved up to Edmonton in the year 2000. I've been an independent investigator, running my own lab in Edmonton University of Alberta since the year 2000. In my eighteenth year now doing research and primarily the research in my lab is investigating cellular excitability, so ion channels that control the behavior of cells whether that be heart cells, whether that be endocrine cells such as in the islets of Langerhans in the pancreas and also do some work on the neuronal regulation as well with respect to certain different ion channels.
02:05: We're an electrophysiology lab and we work on a number of different projects. We're quite eclectic in our approach. We don't just focus on one protein or one ion channel. We try a number of different projects on different ion channels and different tissue types. Really we're trying to understand that link between cellular excitability in health and disease on whether there's any potential to develop therapeutics or strategies in which to reduce the risk of developing disease hone and develop small molecules for treatment of certain diseases. We'd traditionally been focused on diabetes, heart disease and obesity that the major ones who have been working on.
Dan Pardi - 02:45: Tell us a little bit about the work that preceded your current study in the area of melanopsin. What is melanopsin and where do we typically find it in the body?
Peter Light - 02:56: Yeah, as for melanopsin it's an interesting molecule. It's one of the class of opsins of which there is over 200 family members and I guess the most studied area in which they're found is in the postganglionic retinal cells. They're really responsible for the measurement and transduction of levels of blue light that enter the eye so really important in setting that biological clock that we have and many other vertebrates and invertebrates have. It's for basically sensing daylight versus night, setting various circadian rhythms within the body and that signal through melanopsin, which is essentially sensitive to light in the blue and green wavelengths once activated, sets up a signaling pathway, which then may recourse a release of melatonin and you can have that essentially derived signal from the retina being transduced through the brain to periphery to different organs in the body.
03:51: We have the central regulator of circadian rhythm through the retina and mediated by a melanopsin. Then that sends signals to the rest of the body. It had been very well studied in the last couple of decades and our level of interest in it was exactly zero about three years ago. We weren't really studying any of these opsins but through a serendipitous turn of events, which I'm more than happy to tell you about we stumbled upon some really interesting observations that were totally unexpected and then led us down the pathway to begin studying melanopsin in other tissues such as the fat cells beneath your skin.
Dan Pardi - 04:31: We have these photosensitive or light sensitive melanopsin, photopigments that are in the eye or at least classically that's where they've been most studied and they can transduce this light signal into a nerve signal that goes back in the brain, communicates with this master clock and then the master clock can then affect different hormones and gene patterns and behavior and that really helps keep our body in time. Yet, you recently found that these receptors are not only present in the eye but also present in fat tissue and that is unexpected.
Peter Light - 05:04: Yeah that was a totally unexpected finding and I think it's really interesting and fascinating that the background story on how we actually discovered this. We didn't go out and say, "Hey, let's look for light sensitive proteins in fat cells." That was not the original intent but about three years ago, we embarked on a project where we wanted to engineer fat cells to secrete insulin. Really that was because of my work in the diabetes field and being involved as Director of the Alberta Diabetes Institute, which is home to the Edmonton Protocols for islet transplantation, which is our internationally recognized treatment for type 1 diabetes.
05:44: One thing that struck me was that many of the side effects from islet transplantation come from the rejection of those islets. We thought that maybe if we can engineer a patient's own cells to make insulin then we could avoid much of the rejection and the use of immunosuppressant drugs. We struck upon the idea of engineering fat cells, putting the insulin gene in these fat cells and then adding optogenetic sensor. One of these proteins called channelrhodopsin that have been developed primarily for the uses in light activation of neurons so there's a lot of interest in optogenetics these days and we decided to utilize that and put it in the context of trying to engineer fat cells to secrete insulin. That was the original research project that we developed.
06:39: We did these experiments and we engineered the fat cells. We made viral vectors to deliver the insulin gene as well as the channelrhodopsin into fat cells and studying whether we could activate the release of insulin from fat cells by shining blue light on them. As we all do in experiments, we do control experiments, the negative control experiments where we don't transduce the cells with the virus. We do not engineer them and fully expecting to see no light sensitivity whatsoever. However, remarkably in our control experiments we saw reproducible small electrical current in response to blue light stimulation. That really puzzled as you might expect and say, "What's going on here?"
07:29: You kind of go a little bit concerned that it is an artifact in your recording thing. Sometimes if you do electrophysiology you do get small artifacts. These are not very large currents but they are reproducible. I'd probably say my favorite experiment, my cheapest experiment we've ever done was that we got a piece of electrical tape, about half inch in length and we put it over the blue light sensor. The current disappeared and then we pulled off the piece of electrical tape and the current reappeared again. We knew it wasn't an artifact. We looked in the literature extensively to see what's expressed in terms of light sensitive proteins in other tissues apart from the retina especially in tissues say underneath the skin. I know there's a number of opsins expressed within the skin itself but certainly there was very little evidence to suggest they were in any other tissues apart from the retina.
08:27: I guess that really as about two, three years ago when we did that. We spent the last couple of years really characterizing that and that involved a number of different experiments. We did some molecular biology to pull out transcripts so the mRNA message for different opsins and we pulled out predominantly melanopsin very consistently in fat cells.
08:50: The experiment, which I thought was probably the one that clinched it for me was that we contacted several surgeons here in the hospital and we obtained skin and fat samples from humans from cosmetic surgery. We isolated those fat cells from the surgical samples and remarkably again we detected light sensitive currents within these fat cells from humans.
09:17: That was really the background on how we discovered and it was completely serendipitous. I would like to think that with my surname being Light that this was somehow some form of destiny at least at work on this project-
Dan Pardi - 09:31: It must have been.
Peter Light - 09:31: To actually start studying these opsins because it really wasn't in our plan to do this. It was one of those really fun things that happens with discovery-based science is that you never know what you're going to get sometimes and you follow the leads. That's why I get up every morning and come to work is because of the interesting stuff that can just happen in the lab. You basically follow the interesting science. That's how we discovered it and we did a number of different experiments to characterize what the effects of blue light would be on these fat cells. I guess that's the story of our discovery anyway.
Dan Pardi - 10:08: From this understanding now that there was likely these opsin receptors that are in fat tissue, what was your next set of direct experiments looking at this?
Peter Light - 10:18: Yeah, so once we discovered these currents and measured them, we wanted to see if there's any physiological significance of this. I don't know whether yourself or any of your listeners have done experiments on light in the lab. Light is very invasive. It's in everything. You can actually walk around do everything.
10:37: We had to design lab spaces, which were illuminated in very dim light or to put them under red light conditions in the lab in order for us to do these experiments and then calibrate everything in terms of the intensity of light we used. We were very careful that you make an observation that a cell has a photopigment in it but is that light intensity relevant physiologically? I think that was the next step that we took and say, "Okay, what about the light intensities that are required for this?" We did a number of experiments where we changed light intensities and we did back calculations from how powerful the different light sources are. What it actually turns out to be is that it required incredibly bright light source to penetrate the skin with the blue light to actually activate this pathway because only about one to five percent of blue light from sunlight actually penetrates the skin. You've got to have a very bright light source.
11:40: People have been asking me, "Well what about a blue light source or a sunbed or something like this?" I always say, "No, it has to be that big nuclear reactor in the sky. It has to be a very powerful light source to have this effect because only a very small percentage goes through the skin." That was the initial experiment we did.
Dan Pardi - 11:58: What was the intensity capable of getting through the skin to activate these melanopsin receptors in fat tissue? How intense could it be on a cloudy day? Is it any sunlight? Is it morning light, evening light or does it have to be light in midday?
Peter Light - 12:10: Yeah, so what we think is how relevant that is, is that it would most likely be fully activated on a sunny day. It doesn't really matter if the angle of the sun, blue light, tends to penetrate fairly well at different times of the day unlike UV light but we think usual daytime sun is going to have this effect.
12:30: The effect we observed is over a range that you would probably see all through the year but it would probably like has to be a sunny day. Although, we haven't actually done those calculations on cloudy versus sunny day as yet but one could imagine that if it slightly overcast you may still have this effect.
Dan Pardi - 12:49: What did you find when you did shine the adequate intensity of light on the tissue?
Peter Light - 12:54: Next experiments we did were on a populations of cells. We had to design experiments where we could give longer term exposure of blue light to the cells in order for us to actually look at any change in the behavior of these cells. Again we had to basically take over a warm room in the lab and convert it over into an artificial lighting room. Then we had to calibrate the intensities of light coming from a very strong LED light source.
13:28: After we've done a lot of control experiments to calibrate intensities of light where we're sure we were getting the right levels of intensity across all of the cells, we did these chronic light experiments where we exposed populations of fat cells to anywhere between two to four hours of blue light exposure per day. Then at the end of about two weeks of doing this daily exposure, we then measured such things as hormone production, such as adiponectin and leptin, which are two fat derived hormones as well as the ability of these fat cells to store fat in lipid droplets as well as their ability to breakdown fat and release it into the cell medium.
14:15: Our first port of call with this was, "Okay, what's the basic biology of a fat cell and is it effect in?" Obviously, the major one that we all think about is well how much fat can these cells store? What we actually observed is in the blue light treated group is we saw a significant reduction in the lipid droplet size in all of the cells compared to the group of cells that were non-light exposed. That was a really neat observation to actually see a reduction in lipid content. We also observed an increase in fat breakdown or lipolysis in these fat cells. They increased a release of glycerol into the media, which we could measure as well.
14:58: Those two observations suggested strongly to us that the blue light was definitely changing the behavior of these cells and that exposure to relevant intensities of blue light one would expect to penetrate the skin on a sunny day would actually lead to less fat storage in these cells.
Dan Pardi - 15:18: Under the exposure of light there was a decrease in droplet size and a decrease in the number of cells retaining lipid droplets. Do we know any correlation between smaller adipocytes and health parameters?
Peter Light - 15:29: Yeah, so a couple of things we do know about adipocyte size is that the larger the adipocyte, the increase risk there is for localized inflammation, macrophage infiltration, and perhaps development of low grade inflammation, which is a hallmark of certain diseases such as obesity and type 2 diabetes. We also know that enlarged fat cells that over time if they're chronically enlarged, storing too much fat, then they tend to over secrete hormones such as leptin and adiponectin as well. What we consistently saw was a reduction in leptin and adiponectin secretion in cells that were treated with blue light.
Dan Pardi - 16:12: Wow, so interesting. A decrease in lipid droplet size, increase in glycerol release or lipolysis and then a decrease in adiponectin and leptin hormones that are released from the fat tissue, all of these would seem to indicate a change obviously in metabolism of the organism possibly in a favorable way to support metabolic health and it just makes me wonder in a natural environment where there is sparse clothing and lot of daylight exposure is one of the reasons why hunter-gatherer societies are leaner than modern day societies because of this light exposure to the skin. It's some really interesting work recently by Herman Pontzer show that difference in the amount of adiposity that hunter-gatherer societies and modern societies carry does not seem to be due to a change in energy expenditure because there seems to be an accommodation for increased physical activity with reduced energy expenditure. Could this be one of the mediating factors here that's promoting that effect?
Peter Light - 17:05: Yeah, I think what this observation that we made is actually really that provide another piece of the puzzle to exactly what you're talking about. I think that certainly in northern climates where we have further away from the equator anyway that we certainly have seasonal variations in temperature and daylight exposure that this may be a peripheral mechanism that senses that daylight exposure and adjusts fat storage. Maybe as the days get shorter, and we tended to put some more clothes on to keep warmer that we stored more fat not only for insulation but also for energy storage for times when finding food may be more difficult. Yeah, I think we may have come across a potential mechanism, which feeds into that concept that we may have evolved to have a mechanism, which cells regulate fat storage at different times of the year.
Dan Pardi - 17:59: I'm curious to know if this effect would translate into alterations in appetite, energy regulation and microenvironment cellular metabolism all promoting a state of health and better energy balance. It seems plausible. Do you have any interest in studying that specifically in human intervention?
Peter Light - 18:15: Yeah, absolutely. I just actually recently submitted a grant on that and found out yesterday it got funded. Now I have five years of funding to ask exactly those questions. I'm really excited to get going with answering some of those questions. Those underlying mechanisms of what we really need to identify. Our original paper that we published on this was really an observation that blue light changes the phenotype, the behavior of these fat cells. What we already want to know is are there any paracrine effects of these fat cells being exposed to light? Can this translate into some form of messenger that can be picked up and detected by other tissue types, which then further changes perhaps as you mentioned appetite? It all feeds into the idea that these may only be a localized sensor to store fat at different times of the year but it actually may be a really good regulator of other bodily function as well.
19:13: We're absolutely pursuing those possibilities in terms of do these cells that are treated with blue light actually secrete active components, which affects the behavior of neighboring cells or perhaps cells in other tissue compartments within the body? Yeah, absolutely I think there's going to be a huge amount of research in the next few years trying to dissect out what the consequences of this pathway are.
Dan Pardi - 19:37: We could end up with a situation where there is a disagreement between dermatological recommendations specifically stay out of the sun and potentially information that suggest that a certain amount of daily light exposure aside from just helping set your circadian rhythms also is health promoting in that it's affecting metabolism and energy regulation in a healthy way. I look forward to seeing the next steps on that and then also hearing arguments for and against how much sun exposure we should get if this pans out.
Peter Light - 20:05: Yeah, I agree. I think one of the things I've been careful to mention is that I'm not condoning people go out and burn themselves to a crisp to try and lose weight. That's just not what we know about the system right now. We don't know the duration and intensity of light required to elicit this effect once we identify the mechanisms then we can identify at what time points of sunlight exposure these are activated. It's too early to really put a time limit on how much sun exposure we get but I think what this research does is it really does open up that debate about what is an appropriate level of healthy sunlight exposure.
20:41: We all know very well about the effect of sunlight in the generation of vitamin D and we tend to be vitamin D deficient in the winter and replenish our stores as we go outside more and expose our skin but perhaps now we have another additional pathway in which a certain level of sunlight is actually beneficial to our health and conversely a lack of that sunlight during winter months perhaps is actually detrimental to our health.
Dan Pardi - 21:09: Once again, we see here that light is a fundamental constituent of our overall health. Thank you for coming on to humanOS Radio sharing your work. This is one of the most unexpected and interesting studies that I've seen in the last year. I look forward to seeing what the subsequent studies yield.
Peter Light - 21:25: Thank you for giving me the opportunity to talk to you, much appreciated.
Kendall Kendrick - 21:31: Thanks for listening and come visit us soon at humanos.me.