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!

What makes you you? Day of immunology and fun times learning about diversity

What is the feature that distinguishes us from each other, that makes up unique? Most would immediately think of obvious external characteristics like hair or eye colour, but as Professor Daniel Davis explained in a recent lecture I attended, it is actually our immune genes.

Taking us on a whirlwind tour of immunology history, Davis set off by describing the discovery of immune tolerance in 1951 by Medawar and colleagues, who were at the time trying to understand why transplants are rejected. We now know that transplants are rejected because they are recognised as foreign, or 'non-self', by our immune system, and what instructs this recognition are a set of genes known as histocompatibility genes.

The collective work of numerous scientists in the past 60 years has uncovered the shear diversity of histocompatibility genes in the population, how this diversity is integral to our susceptibility to diseases, and the checks and balances present to ensure that this recognition system is working correctly.

But the effects of histocompatibility genes go beyond immunity: more recent work has uncovered fascinating roles for these genes in sexual attraction, with a study finding that women are more likely to be attracted to men with histocompatibility genes that are different from theirs, and even in pregnancy.

The lecture, organised by my old friends at Nature Reviews Immunology, was part of the international Day of Immunology, which first took place on April 29th 2005. Its aim is to celebrate this exciting discipline and raise awareness of its applications, in particular with regard to wellness, to the lay public.

And this is sadly not an easy feat - as Davis noted, there is a dearth of popular science books or TV programmes on immunology, despite it being a subject that has the potential to be of interest to scientists and lay public alike. There is of course a lot of jargon, like any specialist field, and numerous basic concepts that are necessary to understand any new ideas, which has resulted in this crazy idea that immunology is a scary, complicated subject, even among other scientists. Davis urges all immunologists to take steps to become involved and present this exciting discipline to the public (see his Comment piece on Nature Reviews Immunology, which is free for registered users).

His recent book, The Compatibility Gene, will hopefully spur others to explore this field and write more broadly about it. I can't wait to read it! 

PGE2 as a baddie during influenza infection

One of the things that bugs me a lot, in an entirely geeky way, is when people tell me they have the flu - most of the time, they really just have a cold, caused by a completely different pathogen. Influenza, the real cause of flu, can actually cause very serious disease, much more debilitating than a cold virus, and can even lead to death. Case in point: the Spanish flu is thought to have killed more than 20 million people during the first world war, many believe that was responsible for more deaths than the war itself.

Villains
Image from
https://www.flickr.com/photos/kaptainkobold/6900425981/

But I digress. The rant was triggered by a very interesting paper that I spotted in this week's Immunity, which identified a new potential therapeutic target for influenza A: a group of molecules known as prostaglandins.

An involvement for prostaglandins, a group of lipid molecules with many roles including inflammation and immunity, in influenza infection is not new. A quick search in PubMed revealed that members of the prostaglandin family have previously been shown to block influenza replication and limit inflammation, and deficiency in the enzymes responsible for generating the prostaglandin PGE2 (COX1 and COX2) has revealed conflicting results.

Another role for our bacterial masters

Now that I no longer have access to academic papers at whim, I am starting to understand the frustration of those advocating for open access. But I still have my ways, and came across an exciting new story on the gut microbiota in Cell Host Microbe.

If you haven't heard, the gut microbiota (ie the bacteria that naturally live in our gut) is one of the most exciting topics in biology at the moment. In the past decade, it has become clear that we are in fact a 'superorganism', as it is both our genes and the genes of the bacteria that live within us that shape who we are. We are slowly uncovering the numerous roles the gut microbiota has, from regulating the responses of our immune system to controlling the development of our blood vessels, our metabolism and even our behaviour. If you are interested and have access, here is an excellent review  and a viewpoint  article on the topic (ahem, commissioned by me during my Nature Reviews Microbiology days).

3D model of intestinal cells colonised with gut bacteria. Image from the Pacific Northwest National Laboratory obtained on Flickr (https://www.flickr.com/photos/pnnl/8146322408)

And now a study has shown that the gut microbiota doesn't just shape our immune responses, it actually regulates the production of the immune cells that fight pathogens.

Dipping my toe with an immunology blast from the past

You may not know this, but this owlette is a (reformed) scientist. As I have missed looking through cool papers and writing about them, I have decided to take a stab at writing a little science blog here (I have yet to decide on the tone, perhaps it will depend on the paper).

And what best way to start than with a paper from my former lab that I saw this morning in Nature Communications. I realise that I am probably shooting myself in the foot, as this is quite a complicated paper on immunology, a discipline that everyone seems to be scared of and find incredibly confusing. But I never said I didn't like jumping in the deep end! I promise, it is a cool story and I will try and keep it simple.

The immune system is actually a beautifully complicated network of cells (including various types of T cells, B cells, dendritic cells etc) that travel around the highways of the blood stream and lymphatic system to fight infection. It is true, through the years it has become increasingly complicated with the different cell types discovered (bordering on the ridiculous now, I have lost track). But ask any immunologist and they will declare their undying love for their favourite cell type.

How could you not love this T cell beauty? Image from NIAID (https://www.flickr.com/photos/niaid/5950870236/)