Adipose tissue as an immunological organ Implications for childhood obesity

Abstract

Obesity is increasingly considered as an inflammatory disorder. In adults, obesity induces inflammation of adipose tissue (AT). Through the release of inflammatory lipids and immune mediating proteins called adipokines, AT inflammation spreads to other tissues ranging from liver and muscle to the cardiovascular system and circulating immune cells, and drives low-grade systemic inflammation. The low-grade systemic inflammation provides a pivotal link between obesity and its metabolic and cardiovascular sequelae. In a recent Diabetologia paper, we showed that already in obese children, adipose tissue (AT) inflammation occurs (1). Interestingly, the severity of AT inflammation correlates with clinical parameters for insulin resistance. Furthermore, we showed that AT inflammation in childhood obesity drives low-grade systemic inflammation, and affects circulating immune cells such as monocytes, which are known to be involved in the development of atherosclerosis later in life. Taken together, our results suggest that modulating AT inflammation in childhood obesity provides a novel avenue for the prevention of long-term metabolic and cardiovascular disease. Next, we discovered a novel pathway to modulate AT inflammation. As recently published in JCI (2), we showed that AT-resident immune cells such as invariant natural killer T (iNKT) cells play a pivotal role in maintaining healthy adipose tissue. Through direct interplay with lipid-presenting adipocytes, iNKT cells suppress AT inflammation, and prevent systemic inflammation and insulin resistance in mice and humans. Knockout or antibody-mediated depletion of iNKT cells in mice has a devastating impact on AT inflammation and insulin resistance, while ligand-mediated stimulation of iNKT cells prevents metabolic derailment in obesity. Summarizing, our results show that modulation of iNKT cell function may prevent metabolic and cardiovascular complications in obese patients, including children. In conclusion, considering childhood obesity as an inflammatory disorder offers a novel perspective on the prevention of long-term metabolic and cardiovascular complications. Immune modulatory interventions show promise for the near-future, though their safety, cost-effectiveness and implementation in the integrative treatment of childhood obesity require careful consideration