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.