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!

Its good to talk, especially in the case of fat cells and skin cells

To get anywhere, you need effective communication, be it between say construction workers building a bridge (as a human example), worker bees making honey or bats out in the dark hunting for food. The same applies in the micro scale - the cells in our body need to communicate at different stages of development so that they know what to become, where to go, whether to grow or die, among other things.

Its good to talk.
 Image from https://www.flickr.com/photos/danielcoy/4175199668

And just like many other cells in the body, adipocytes (or fat cells; a slight obsession of mine in my previous life!) communicate with a type of skin cell known as a keratinocyte, sending signals to regulate the growth of hair follicles and, ultimately, hair growth (a very complicated cycle of growth and death that you can read about here if you have access). It turns out that this line of communication actually goes both ways, as a new study published in PNAS shows that molecular signals from epidermal cells also regulate the growth of the underlying adipocyte layer.