Immune system and obesity

Obesity is a major risk factor for many serious diseases such as cardiovascular disease, diabetes, and cancer. The increasing incidence of obesity focuses attention on the need for mitigating obesity.

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Inflammation is a major contributor to many of these diseases and prevention of obesity-induced inflammation should be a key priority in tackling the obesity burden. Immunological alterations caused by obesity are pivotal mediators in the chronic inflammation that drives obesity-induced metabolic disorder.

iNKT cells are innate T cells of the immune system that are highly conserved in mammals. Unlike adaptive T cells that recognise peptides, iNKT cells recognise lipid antigens. The EU-funded 'Omental iNKT cells as an immunological tools in obesity and cancer' (INKT CELLS) project aimed to investigate the role of iNKT cells in fat tissue and devise novel therapeutic strategies.

Researchers found that iNKT-deficient mice on a normal diet were obese. On a high fat diet they gained weight faster and displayed rapid and severe insulin resistance and type 2 diabetes. Adoptive transfer of iNKT cells into iNKT-deficient mice improved glucose metabolism. These studies demonstrated that iNKT cells maintain healthy adipose tissue under normal conditions and correct obesity under high fat diet conditions. However, in obese humans and mice these iNKT cells are greatly reduced, and therefore their protective effects may be lost.

Using parabiotic experiments, researchers showed that this iNKT cell subset is resident in adipose tissue. Expression profile of these cells included transcription factors that are responsible for their unique function, especially interleukin (IL)-2 and IL-10 production. Through production of these cytokines, iNKT cells control adipose Treg and other T cell survival, proliferation and suppressor functions.

Researchers obtained strong evidence that human and murine adipose tissues contain lipid antigens recognised by iNKT cells. Currently investigation is underway to identify these specific lipids.

Obesity and obesity-associated diseases are increasing at a staggering rate in the western world and this project has clear socio-economic impact. The ability to selectively activate adipose iNKT cells provides an entirely new therapeutic direction for treating obesity and type II diabetes.

Keywords

Obesity, diabetes, inflammation, iNKT cells, innate T cells, adoptive transfer, parabiotic, IL-2, IL10, cytokines