iNKT Cells Reduce Obesity

Sci. Signal.  25 Sep 2012:
Vol. 5, Issue 243, pp. ec249
DOI: 10.1126/scisignal.2003632

Invariant natural killer T (iNKT) cells are a subset of lymphocytes that function as part of the innate immune response. They respond to lipid antigens, such as alpha-galactocylceramide (αGC), and can produce both proinflammatory and anti-inflammatory cytokines (see the commentary by Lukens and Kanneganti). Following up on earlier work that showed that iNKT cells are enriched in human adipose tissue but become less abundant with increasing obesity, Lynch et al. showed that iNKT cells were also enriched in adipose tissue in mice but were reduced in number in mice fed a high-fat diet compared with those in mice fed a standard diet. Mice deficient in iNKT cells gained more weight on a high-fat diet than did wild-type mice, despite not eating more food, and they exhibited increased serum glucose concentrations and decreased insulin sensitivity. The numbers of proinflammatory macrophages in the adipose tissue of wild-type mice increased during the development of obesity and were inversely correlated with the numbers of iNKT cells present. Transfer of iNKT cells to obese iNKT cell–deficient mice resulted in weight loss and a reduction in adipocyte size compared with that in iNKT cell–deficient mice that did not receive iNKT cells. Obese wild-type mice that were injected with αGC lost weight and had smaller adipocytes than did similarly treated obese iNKT cell–deficient mice. Treatment with αGC resulted in an increase in the number of iNKT cells and in the amounts of anti-inflammatory cytokines in the adipose tissue. Together, these data suggest that iNKT cells protect against diet-induced obesity by inhibiting inflammation in the adipose tissue, and they raise the possibility of the use of iNKT cell–targeted therapies for the treatment of obesity.

L. Lynch, M. Nowak, B. Varghese, J. Clark, A. E. Hogan, V. Toxavidis, S. P. Balk, D. O’Shea, C. O’Farrelly, M. A. Exley, Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37, 574–587 (2012). [PubMed]

J. R. Lukens, T.-D. Kanneganti, Fat chance: Not much against NKT cells. Immunity 37, 447–449 (2012). [Online Journal]