A UV addiction through endorphins?

Ah, summer, with its warm weather and abundant sunshine, is finally here - well, sort of if you live in the UK. Sun worshipers crowd patches of grass at every opportunity, desperate to catch some heat and, with any luck, the lovely, healthy glow of a tan.

Image from https://flic.kr/p/4dnzTq

Apparently, according to a recent Cell paper, the uncontrollable urge to go sit out in the sunshine to catch some rays (or go lie in a tanning 'coffin' if so inclined) can actually be explained by an addiction to UV light.

When we are exposed to UV light, the DNA in our skin cells, or keratinocytes, becomes damaged, which triggers the activation of a pathway that results in the production of a protein known as proopiomelanocortin (POMC). This is processed into a hormone, known as α-MSH, that stimulates the tanning process. It is also processed into β-endorphin, an endogenous opioid that offers similar analgesic effects to exogenous opiods, partly by binding to μ-opioid receptor.

The research group from Harvard Medical School saw that exposing rats to UV light triggered the production of  β-endorphin, as they expected. What was intriguing, however, was that this seemed to correlate with a higher pain threshold, something that could be blocked through treatment with the opioid antagonist naloxone, a drug that is used to counter the effects of opioid overdose.

What is more, treating these rats with naloxone triggered what the researchers describe as "classic murine signs of opioid withdrawal" - apparently that's "wet dog shake, paw tremor, teeth chatter and rearing". This suggests that the rats were developing an addiction, of sorts, to the β-endorphin released after UV exposure.

Notably, the increased pain threshold and withdrawal symptoms were not observed in rats lacking β-endorphin, which highlights it as the 'causative' factor behind these symptoms.

So there you have it - the release of β-endorphin seems to be causing a UV light addiction, complete with withdrawal symptoms. Although the work was carried out in rats, a similar addictive behaviour may apply to humans as well and may explain, in a more biological way, why many of us continue to expose ourselves to high levels of UV light despite knowing that it can give us skin cancer.

Who said beige is boring? The secrets of good fat, and more evidence that the immune system is behind everything

We have all been conditioned to believe that all fat is bad, but this is not actually the case. We are born with what is known as brown fat, which actually burns energy by generating heat, or thermogenesis, to protect us from the cold. But this is gradually replaced with white fat, the fat that we all consider to be bad. However, some white fat can be converted into brown fat when exposed to cold or intense exercise; in this case, the brown fat is called beige, or brite, fat.

Bad but tasty fat!

With obesity in an all-time high, there is obviously great interest in understanding the mechanism behind this conversion process and potentially use it to develop therapeutics. Two independent studies published in Cell now identify a link between the development of beige fat and the immune system.

The first group, led by Professor Bruce Spiegelman, found that the levels of the hormone Metrnl (Meteorin-like) increases in the bloodstream after exposure to cold or exercise, and injection of this hormone in mice resulted in the expression of brown fat genes and reduction of fat content.

Metrnl must somehow trigger the switch to beige fat - this is where the immune system fits in and where the two studies overlap. Using genetically modified mice, the second group, led by Professor Ajay Chawla, saw that interleukin-4 (IL-4) and IL-13, two immune molecules known as cytokines, can also stimulate the conversion of white fat into beige fat. And, as shown by Spiegelman's group, Metrnl stimulates an increase in the levels of these cytokines.

Both groups went on to show that IL-4 and IL-13 in fat tissue are produced by immune cells known as eosinophils, which are famous for their roles in combating parasite infections but are also culprits in the pathology of asthma and allergies.

In this case, eosinophils produce IL-4 and IL-13, which trigger the development of alternatively activated, or M2, macrophages, another immune cell type that is involved primarily in tissue repair. These cells then produce a group of molecules known as a catecholamines that can trigger the expression of the genes that convert white fat to beige fat, ultimately giving rise to beige fat development.

Could targeting the immune system offer a solution to obesity and metabolic diseases such as diabetes? The results of the two studies suggest that targeting this pathway may be promising. Spiegelman's group found that injecting mice with Metrnl decreased their body fat content, and could improve glucose tolerance in obese diabetic mice. Along similar lines, Chawla's group found that injecting obese mice with IL-4 decreased fat mass and could restore insulin sensitivity.

So, once again the immune system is the 'conductor', orchestrating the conversion of beige fat from white in times of stress such as cold, and holding the key to a not-so-boring type of beige, ie the kind that makes us lean!