Interleukin-15, IL-15 Receptor-Alpha, and Obesity : Concordance of Laboratory Animal and Human Genetic Studies

Abstract EN

Interleukin-15 (IL-15) is a cytokine which inhibits lipid deposition in cultured adipocytes and decreases adipose tissue deposition in laboratory rodents.

In human subjects, negative correlations between circulating IL-15 levels and both total and abdominal fat have been demonstrated.

Deletions of IL15 in humans and mice are associated with obesity, while gain-of-function IL-15 overexpressing mice are resistant to diet-induced obesity.

IL-15 is highly (but not exclusively) expressed at the mRNA level in skeletal muscle tissue, and the regulation of IL-15 translation and secretion is complex.

Conflicting evidence exists concerning whether circulating IL-15 is released from skeletal muscle tissue in response to exercise or other physiological stimuli.

The IL-15 receptor-alpha (IL-15Rα) subunit has a complex biochemistry, encoding both membrane-bound and soluble forms which can modulate IL-15 secretion and bioactivity.

The gene encoding this receptor, IL15RA, resides on human chromosome 10p, a location linked to obesity and type-2 diabetes.

Several single-nucleotide polymorphisms (SNPs) in human IL15RA and IL15 correlate with adiposity and markers of the metabolic syndrome.

Genetic variation in IL15RA may modulate IL-15 bioavailability, which in turn regulates adiposity.

Thus, IL-15 and the IL-15Rα may be novel targets for pharmacologic control of obesity in the human population.