October 19, 2021

I, Science

The science magazine of Imperial College

The link between a functional immune system and our fat stores deepens

fat burgerImmune cells can help reduce the risk of obesity, according to a recent study published in Nature.

Dr David Artis and his team found that a type of immune cell known as group 2 innate lymphoid cells (ILC2s) is present in higher numbers in non-obese compared with obese humans and mice and can stimulate the conversion of white fat cells into beige fat cells. Unlike white fat cells, beige fat cells actually burn energy by generating heat (thermogenesis) and have previously been shown to arise from white fat cells through, for example, cold exposure or exercise.

Key to the ILC2-mediated conversion of white fat into beige fat is a molecule known as interleukin-33 (IL-33), a cytokine (small protein involved in cell signalling) that promotes the activation and expansion of ILC2s in many tissues, and lack of which is linked to fewer beige fat cells and increased adiposity. The researchers saw that stimulation of ILC2s with IL-33 in mice triggers their production of the peptide methionine–encephalin (MetEnk).This, in turn, promotes the expression of Uncoupled Protein 1 (UCP1), a protein that is expressed by beige fat cells and is key for the thermogenic process that burns calories.

With the growing problem of obesity worldwide, there is great interest in learning more about beige fat and what triggers its conversion from white fat. It is now evident that the immune system has a key role in this process. For instance, earlier in 2014 two independent studies showed that another type of immune cell, eosinophils, can trigger the development of beige fat cells through the production of the cytokines IL-4 and IL-13. Although ILC2s can promote the development of eosinophils, here Dr Artis and his team show that ILC2s promote conversion of beige fat from white fat cells directly, through a distinct mechanism.

Why does the immune system regulate fat homeostasis? The researchers postulate that such a mechanism “could provide a rapid, integrated multi-organ response that allows mammals to surmount multiple environmental challenges including infection, nutrient stress or changes in temperature”.

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