the increased incidence of obesity in both developed and developing nations is a major public health problem .
altered energy balance resulting in obesity is believed to be causal in the development of the metabolic syndrome and type-2 diabetes mellitus , conditions whose incidence is also rising at alarming rates [ 2 , 3 ] .
is currently in excess of $ 200 billion annually , and it is expected to rise . diet and lifestyle modifications are often unsuccessful in reducing obesity [ 46 ] , and presently available pharmacologic treatments are problematic due to serious adverse effects .
evidence that interleukin-15 ( il-15 ) can inhibit adipose tissue deposition in both laboratory animals and human subjects will be reviewed .
the specific receptor for il-15 , il-15 receptor - alpha ( il-15r ) , appears to regulate il-15 secretion , stability , and activity [ 8 , 9 ] .
several single - nucleotide polymorphisms ( snps ) in human il15 and il15ra have been described which correlate with adiposity and markers of the metabolic syndrome [ 1012 ] .
these findings suggest a model in which genetic variation in il15ra could modulate il-15 activity and bioavailability , which in turn regulate adiposity . moreover , because il-15 mrna is highly expressed in skeletal muscle tissue , some authors have suggested that il-15 may function as a muscle - derived endocrine factor , or 
when human genetic , cell culture , and laboratory animal studies are taken together , it is clear that the il-15/il-15r axis regulates adiposity .
modulation of this axis should be explored a novel target for control of obesity in the human population .
il-15 is a 14  kda cytokine that was originally isolated on the basis of its ability to support natural killer ( nk ) t - lymphocyte proliferation .
il-15 was subsequently found to be expressed by monocytes , macrophages , and other cell types involved in immunity and to regulate a variety of processes comprising both innate and adaptive immunity reviewed in .
il-15 exhibits both pro- and anti - inflammatory actions in a variety of tissues and has both positive anticancer effects via stimulation of nk cells , and deleterious effects such as involvement in inflammatory bowel disease ( reviewed in [ 18 , 19 ] ) .
inasmuch as the present paper is focused on the relationship of il-15 to obesity , the reader is referred to comprehensive reviews of the diverse functions of il-15 provided by fehniger and caligiuri   and budagian et al . .
il-15 is structurally part of the 4-helix bundle protein family , whose members   exhibit structural , but not necessarily sequence , homology .  
this family of proteins includes many cytokines which regulate the immune system and also includes factors with actions outside of the immune system , such as il-6 , leptin , growth hormone , and erythropoietin .
il-15 is expressed at the mrna level in a variety of nonlymphoid tissues , with particularly high expression in skeletal muscle and placenta .
il-15 is also expressed abundantly in cardiac muscle , lung , liver , kidney , brain , and pancreas . in the placenta
, il-15 regulates a specific subset of nk cells involved in endometrial decidualization . in nonlymphoid tissues ,
conflicting reports [ 14 , 24 ] exist regarding il-15 mrna expression in cultured adipocytes ( reviewed below ) , and a systematic study of il-15 expression in adipose tissue in vivo has not been conducted .
both humans and laboratory mice exhibit detectable levels of il-15 in the circulation , ( for example , [ 9 , 10 , 15 , 25 ] ) , allowing for the possibility that il-15 can exert endocrine ( as well as paracrine ) effects on cell types which do not express il-15 itself .
because of the high expression of il-15 in skeletal muscle and evidence that other cytokines such as il-6 are released from muscle following physical activity , some investigators have suggested il-15 functions as a myokine which exerts positive effects on body composition via an endocrine mechanism [ 1316 ] . conflicting evidence for il-15 as a myokine is reviewed below .   as mentioned above , another tissue which exhibits high expression of both il-15 mrna and protein is placenta [ 17 , 26 , 27 ] . in a study comparing concentrations of numerous cytokines in amniotic fluid and sera of normal pregnant women , chow et al .  
reported significantly higher il-15 concentrations in serum than in amniotic fluid , consistent with literature indicating many cytokines do not cross the placental barrier .
however , studies of whether gravid animals or pregnant women display increased circulating levels of il-15 compared to nongravid or nonpregnant females are lacking . in any case , such an observation would not apply to males and does not preclude skeletal muscle or other tissues as additional sources of il-15 in both genders .  
two il-15 mrna isoforms are generated from a single il15 gene in humans and mice [ 28 , 29 ] .
the two isoforms differ in the lengths of the signal peptides and have been designated long signal peptide ( lsp ) and short signal peptide ( ssp)-il-15 mrna .
however , tissue expression and intracellular trafficking of these isoforms are dissimilar [ 28 , 29 ] . ssp - il-15 mrna is highly transcribed in heart , and also expressed in thymus , testes , and appendix , whereas lsp - il-15 mrna is transcribed strongly in skeletal muscle and placenta , and at lower levels in heart , lung , liver , thymus , and kidney .
ssp - il-15 does not appear to be secreted , and either functions intracellularly or is released following cell damage [ 28 , 29 ] .
lsp - il-15 is secreted ; however , the unusually long 48 amino acid signal peptide renders il-15 secretion extremely inefficient [ 2831 ] .
lsp - il-15 protein translation is impeded by multiple augs ( initiation codons ) in the 5 untranslated region [ 3133 ] . because of the inefficiency of il-15 translation and secretion , correlations between il-15 mrna levels and secretion of il-15 protein are often weak ( reviewed in [ 18 , 33 ] ) .  
a systematic comparison of il-15 protein expression among tissues has not been conducted , and it is technically difficult to demonstrate secretion from a specific tissue in vivo , particularly in mouse models .  
the mouse 3t3-l1 adipogenic cell line does not express levels of il-15 mrna detectable by highly sensitive real - time pcr at any stage of differentiation .
however , another study demonstrated primary pig adipocyte cultures express il-15 mrna at low basal levels , which are upregulated following stimulation with interferon- . whether il-15 protein was produced or released into the culture medium
differences between rodents and swine , and/or between adipogenic cell lines and primary cultures , as well as between adipocytes in vivo and in vitro , are quite possible .   in obesity , adipose tissue develops an inflammatory environment due to infiltrating macrophages which are a source of numerous proinflammatory cytokines [ 34 , 35 ] . in a mouse strain highly susceptible to oxidative stress , high dietary calcium in conjunction with an obesigenic diet significantly stimulated il-15 mrna expression in both visceral fat and skeletal muscle tissue , but it was not determined which cell types were responsible for the upregulated il-15 message . a systematic study of il-15 mrna and protein expression in various depots of fat tissue , in different physiological conditions , has not been performed .
thus , whether adipocytes and/or adipose tissue can express and secrete il-15 protein in basal conditions or in inflammatory challenges associated with obesity remains unclear .
the il-15 gene ( il15 ; human accession number u14407 ) is mapped to human chromosome 4q31 and the central region of chromosome 8 in mice . a recent genome - wide survey of human copy number variations which correlated with
obesity revealed a large ( 2.1  mb ) deletion of a region which included both il15 and the gene encoding the mitochondrial uncoupling protein ucp1 .
since the role of ucp1 in modulating energy balance is well described , the potential contribution of loss of il15 by this large deletion was not additionally considered .
however , research findings from adipogenic cell cultures , laboratory animals , and human subjects all suggest il-15 may also function as an antiobesigenic factor .   in a study of human subjects comprising a wide range of body mass indices ( bmi ) , nielsen et al
.   found negative associations between plasma il-15 concentrations and bmi ( p < .001 ) , total fat mass ( p < .001 ) , trunk fat mass ( p < .01 ) , and limb fat mass ( p < .05 ) .
negative associations between muscle il-15 mrna and obesity parameters were also observed in that study .  
a similar finding was reported by barra et al .   who observed obese human subjects exhibited lower circulating il-15 levels than lean subjects .
however , christiansen et al .   reported decreased circulating il-15 concentrations following diet - induced weight loss in obese human subjects .
two snps in human il15 ( rs1589241 and rs1057972 ) are associated with various predictors of the metabolic syndrome , bmi , and muscle strength [ 10 , 11 ] .
these snps are located in the 5 and 3 untranslated regions ( utrs ) of the gene , suggesting they could modulate il-15 expression .
mice with targeted deletion of il15 ( il-15ko mice ) exhibit higher amounts of body fat than control mice .
conversely , transgenic mice which were engineered for elevated circulating levels of il-15 ( il-15 tg mice ) , expressed from a skeletal muscle - specific promoter , exhibited lower levels of body fat than closely related controls , and were resistant to diet - induced obesity .
in the same study , mice which expressed high intramuscular levels of il-15 but which did not exhibit elevated serum il-15 levels showed no differences in adiposity compared to controls , suggesting il-15 must be secreted into the circulation to exert its effects on adipose tissue . since this is an artificially constructed system , it can model , but does not prove , the hypothesis that muscle - derived il-15 acts as a myokine in the native state .  
il-15 has also been introduced into wild - type laboratory rodents by injection of recombinant il-15 protein [ 13 , 40 ] , by adenoviral expression vectors , and by dna electrotransfer into skeletal muscle . in these studies ,
il-15 administration reduced fat mass by as much as 30% in normal rodents and 10% in obese rodents .
importantly , inhibition of fat deposition was observed in the absence of an effect of il-15 on food consumption [ 13 , 40 ] .
additionally , in the studies of both il-15ko mice and the gain - of - function il-15 tg mice described above [ 40 , 42 ] , no effects of loss or overexpression of il-15 on food intake were observed .
therefore , the effects of il-15 on adipose tissue are not likely to be due to an indirect effect of modified energy intake . however , one report indicated chronic treatment of rats with il-15 slightly inhibited intestinal absorption of triaclglycerols specifically .
lean body mass is unaffected by il-15 [ 13 , 40 , 42 ] , indicating il-15 does not induce a cachectic state ; indeed , recombinant il-15 injection can prevent loss of skeletal muscle mass in rodent models of cancer cachexia .
il-15 injection inhibited fat deposition in both wild - type and leptin - deficient obese ( ob / ob ) mice .
il-15 administration to lean rats also inhibited fat deposition , but it was unable to inhibit fat deposition in leptin receptor - deficient obese ( fa / fa ) zucker rats .
obese , but not lean , rats exhibited significant decreases in adipose tissue expression of mrna for two of the subunits of the heterotrimeric il-15 receptor , the il-2 receptor beta and   gamma subunits ( il-2r and il-2r ) , while expression of adipose tissue il-15r mrna was unchanged .
this observation suggests that adipose tissue of obese zucker rats failed to respond to il-15 because the signaling subunits ( il-2r and il-2r ) of the il-15 receptor were downregulated in adipose tissue in this strain , and that the effect of il-15 on adipose tissue is direct .
the direct effect of il-15 on adipose tissue was confirmed using adipogenic cell cultures derived from several mammalian species , including human [ 14 , 40 , 46 ] .
recombinant il-15 administration inhibited preadipocyte differentiation and lipid deposition in the immortalized mouse 3t3-l1 cell line .
moreover , in differentiated 3t3-l1 adipocytes , il-15 dose - dependently stimulated secretion of the insulin - sensitizing and antiobesigenic factor adiponectin .
similar results were observed by another laboratory using cultured primary porcine adipocytes , in which il-15 potently stimulated lipolysis and modestly inhibited lipogenesis .
finally , barra et al .   found that administration of il-15 to lipoaspirate - derived human adipocyte cultures inhibited lipid deposition .
the molecular pathways mediating the effects of il-15 on adipose tissue have not been characterized in detail .
one study   suggested il-15 upregulates expression of calcineurin mrna , a factor which inhibits adipocyte differentiation .
in contrast to adipose tissue , il-15 mrna and protein expression has been observed consistently in skeletal muscle and skeletal muscle - derived culture systems [ 23 , 4851 ] , where it functions to modulate myofibrillar protein dynamics [ 23 , 44 ] . at the protein level
, il-15 has been immunolocalized to human skeletal muscle fibers in tissue sections which contained few il-15-positive infiltrating cells .
detected il-15 protein by immunohistochemistry and western blotting in human skeletal muscle with both type-1 and type-2 fiber dominance , which did not correlate with the respective levels of il-15 mrna expression in these muscles .
expression of il-15 mrna and biologically active il-15 protein has been detected in primary human myogenic cultures , human rhabodomyosarcoma - derived cell lines , and a rat clonal myogenic cell line .
il-15 mrna expression is low , but detectable , in mouse c2c12 skeletal myogenic cultures at the myoblast stage , but it is induced about 10-fold upon differentiation . therefore , published evidence indicates il-15 is expressed by skeletal muscle fibers themselves , not vascular , connective tissue , or lymphoid infiltrating cells present in muscle and in primary cultures .
however , it is unclear if these observations translate to meaningful contributions to circulating il-15 levels by skeletal muscle tissue .   
several cytokines , most notably interleukins 6 , 8 , and 10 , are released from skeletal muscle following physical activity , resulting in large changes in plasma concentrations of such  myokines  [ 52 , 53 ] .  
one study found that in human skeletal muscle , il-15 was the mostly highly expressed of all cytokines measured at the mrna level . since both il-15 and physical exercise have positive effects on body composition , it is reasonable to hypothesize il-15 release following exercise may mediate some of the beneficial effects of physical activity [ 16 , 54 ] .
however , there are conflicting reports as to whether physical activity affects il-15 expression in skeletal muscle and/or increases circulating il-15 levels . in a study of young untrained and 10-week - trained human subjects ,
riechman et al .   demonstrated an increase in plasma il-15 protein levels immediately following whole - body resistance exercise and speculated that il-15 was released following exercise via microtears in muscle fibers .
however , there was no effect of training on the postexercise release of il-15 in that study , casting doubt upon muscle damage as the mechanism .
in contrast , a similar study using untrained human subjects reported no increase in muscle or circulating il-15 protein levels at intervals from 6 to 48 hours following an intensive resistance exercise protocol which involved only the quadriceps muscles ; however , increases in quadriceps muscle il-15 mrna expression were observed 24 hours after exercise .
discrepancies between these studies may be due to the differences in the intervals between exercise and blood sampling .
prior training or physical condition may modulate the purported release of il-15 from skeletal muscle tissue by exercise .   using strength - trained human subjects , nieman et al .  
similarly , ostrowski et al .   observed no changes in plasma il-15 following 2  h of treadmill running by 2 male athletes , and andersson et al .   found no acute effects of competition on il-15 levels in elite female soccer athletes .
in contrast , using sedentary postmenopausal women , prestes et al .   reported an increase in plasma il-15 levels 48 hours following the first session of resistance training but no effect following 16 weeks of training .
finally , christiansen et al .   studied chronic ( not acute ) plasma cytokine levels in obese , physically inactive subjects subjected to a program of intensive ( hypocaloric ) dietary intervention , aerobic exercise , or the combination of diet and exercise .
compared to baseline , diet alone and the combination of diet and exercise significantly decreased circulating il-15 levels , whereas aerobic exercise alone had no effect . however , given the extremely hypocaloric nature of the dietary intervention ( 600800  kcal / day ) , it is possible some loss of muscle tissue occurred , which was not examined
similarly reported no effect of a 12-month program of combined aerobic , strength and balance intervention on circulating il-15 levels in frail elderly subjects .
it is possible that differences among these studies were due to the use of highly trained versus untrained , obese , and/or elderly subjects and/or to the difference between aerobic versus resistance exercise .
therefore , evidence for the hypothesis that il-15 is released following exercise is mixed and largely negative .
moreover , an increase in circulating il-15 levels after exercise is only circumstantial evidence of its derivation from skeletal muscle tissue .
for example , although skeletal muscle expresses the myostatin - inhibiting factor follistatin , a recent study provided evidence that the postexercise rise in circulating follistatin is mostly likely derived from the liver rather than from muscle tissue .  
the concept of il-15 as a  myokine  does not necessarily imply that it is released by exercise , rather it implies simply that the factor is derived from skeletal muscle tissue and is released in quantities sufficient to have an endocrine effect on other cell types .
such release also does not necessarily imply that expression of the purported myokine is specific to skeletal muscle tissue . on the other hand ,
skeletal muscle tissue comprises almost 50% of body mass and is specialized for protein synthesis , if not secretion , so a small release of a bioactive factor from each muscle could have a large systemic effect .
sporadic reports of other inflammatory , hormonal , or nutritional factors which affect muscle il-15 mrna expression and circulating il-15 protein levels have been published .
administered the synthetic progestin megestrol acetate at 800  mg / d for 12  wk , with or without testosterone ( 100  mg / wk ) , resistance training , or the combination of resistance training and testosterone .
progestin ingestion , but no other treatment , caused highly significant increases in circulating il-15 levels , but this treatment did not correlate with changes in muscle mass or body composition .
as mentioned above , dietary calcium significantly stimulated il-15 mrna expression in murine skeletal muscle tissue ( as well as visceral fat ) in obesigenic conditions and oxidative stress , which was interpreted as an increase in anti - inflammatory cytokine expression due to calcium - mediated inhibition of 1,25-dihydroxyvitamin d3   .  
in myogenic cell cultures , overexpression of an orphan nuclear hormone receptor which is highly expressed in muscle , retinoid - related orphan receptor gamma , upregulated both il-15 and myogenin mrna , as well as expression of several genes which regulate lipid and carbohydrate metabolism , insulin sensitivity , and reactive oxygen species .
cultured rat myocytes upregulated il-15 mrna in response to both the inflammatory factor interferon- and the anti - inflammatory cytokine il-4 , while primary human myoblast cultures increased expression of both intracellular and secreted il-15 protein in response to several inflammatory mediators ( interferon- , interleukin-1 , interleukin-1 , tnf- , and lipopolysaccharide ) .
these observations suggest muscle il-15 expression is modulated by dietary , hormonal , and inflammatory status , but , as in the experiments dealing with exercise , a clear understanding of the regulation of il-15 expression by such factors in skeletal muscle tissue is lacking .
increased age is an important predictor of obesity and the metabolic syndrome [ 3 , 62 ] .
reports in animal models on the effects of age on il-15 expression in muscle and in serum are conflicting .
.   found that il-15 mrna was elevated in both slow and fast aging rat muscles compared to young muscles .
the same study found that il-15 mrna was elevated in atrophied slow soleus muscles of young rats but not in the fast plantaris muscle .
a similar effect of aging and immobilization recovery on il-15 mrna in rat muscles was reported in another study .
however , given the complex regulation of il-15 described above , it is unclear whether these changes in il-15 mrna expression reflect similar changes in muscle il-15 protein expression and secretion in these physiological states . indeed , in mice , both muscle and serum il-15 protein levels were reported to decline progressively with increasing age ; however , this decline was not accompanied by decreases in transcription of either ssp- or lsp - il-15 mrna .
rather , while expression of the membrane - associated form of il-15r ( mbil-15r ) did not change with age , an age - related decline in expression of muscle soluble il-15r ( sil-15r ) mrna in muscle tissue was demonstrated , suggesting decreased expression of this factor ( reviewed below ) could lead to age - related declines in il-15 secretion from muscle .
in another study , a similar decline in muscle il-15 protein levels ( and muscle il-15r mrna expression ) in ad lib - fed rats was described , but no declines in il-15 protein levels or il-15r mrna expression were observed in long - lived , calorie - restricted rats .   intriguingly , gangemi et al .   observed that while serum il-15 concentrations exhibited a downward trend with age in unselected human subjects , individuals with unusually long lifespans ( 95 to more than 100 years ) and still living independently had significantly elevated circulating il-15 levels , suggesting elevated il-15 levels conferred some protection against age - related illness .
il-15 signaling is transduced either through a heterodimeric receptor comprising il-2r and il-2r , or through a heterotrimeric receptor comprising mbil-15r plus il-2r and il-2r .
the il-2r and il-2r subunits are responsible for signal transduction , while mbil-15r has only a short cytoplasmic region and functions primarily to confer high - affinity binding to the receptor complex .
cells can express heterodimeric and heterotrimeric il-15 receptor complexes simultaneously or express il-15r in the absence of the other two subunits .
unexpectedly , mice in which the il-15r is deleted ( il15rko mice ) are leaner , rather than fatter , than controls .
this observation suggests a complex role for this receptor subunit in control of body fat , and is consistent with the idea that the il-15r can function in roles other than a membrane - bound receptor component .
il15ra ( human accession number u31628 ) is located on mouse chromosome 2 and human chromosome 10p .
loci on human chromosome 10p have been strongly linked to both obesity and type-2 diabetes [ 70 , 71 ] .
human and mouse il15ra exhibit similar genomic structures ( [ 67 , 69 ] and reviewed in ) .
il15ra has an efficient signal sequence ( exon 1 ) , a ligand - binding domain ( exon 2 ) , a transmembrane domain ( exon 6 ) , and , as mentioned , a fairly short cytoplasmic domain ( exon 7 ) .
exon 2 encodes a conserved protein - binding region known as a  sushi  domain , which is responsible for the binding affinity of il-15r for the il-15 ligand [ 67 , 69 ] .
a number of il-15r mrna splice variants have been reported in both mouse and human , some of which encode soluble forms which may modulate il-15 secretion and bioavailability . because both isoforms of il-15 have inefficient signal sequences , recent experimental evidence suggests il-15 is brought to the cell surface by intracellular association with either sil-15r or mbil-15r , both of which would include the efficient exon-1-encoded il-15r signal sequence .
one , which arises by differential splicing , comprises only exons 1 and 2 , so does not contain a transmembrane domain .
il-15 secretion as an il-15/sil-15 r complex is thereby facilitated following intracellular binding of il-15 and this truncated receptor isoform [ 8 , 9 ] .
another form of sil-15r arises by proteolytic cleavage of mbil-15r ( which can be complexed to il-15 ) by the matrix metalloproteinase tnf- converting enzyme ( tace ) .
release of this form of circulating il-15/sil-15r complex is dependent upon tace activity , which in turn is correlated with obesity and insulin resistance in mice and humans [ 73 , 74 ] .  
uncomplexed il-15 and the two types of il-15/sil-15r complexes appear to be in a dynamic equilibrium in the circulation , and the two soluble receptor variants can compete for binding of il-15 .
however , while both forms facilitate il-15 secretion and can increase il-15 half - life in the circulation , the two variants have differential effects on il-15 bioactivity ; additionally , the two types of il-15/sil-15r complexes can differentially bind heterodimeric versus heterotrimeric il-15 receptors [ 8 , 9 ] .
therefore , regulation of the various forms of sil15r may be an important element modulating il-15 secretion and bioactivity .   in this
regard , human genetic studies by three separate laboratories have identified several single - nucleotide polymorphisms ( snps ) in il15ra which impact muscularity , fat deposition , and markers of the metabolic syndrome [ 13 , 14 , 19 ] .
for example , a snp ( rs2228059 ) in exon 3 correlates with serum triglyceride levels in males .
an a to g variation in the exon 5/intron border ( snp accession rs3136618 ) is associated with the so - called normal weight obese / de lorenzo syndrome , characterizing young women with normal bmis but greater than 30% body fat and the presence of several markers of metabolic syndrome . in a separate study of male subjects by a different group , this same snp correlated with muscularity .
whether il-15 is differentially complexed with sil-15r variants during obesity has not been studied , but the existence of multiple snps in il15ra which correlate with body composition suggest this is a fertile area for future investigation .
il-15 and il-15 receptor subunits are expressed in several regions of the cns [ 68 , 75 , 76 ] .
il-15 has been reported to modulate non - rem sleep   and to play a protective role in neuroinflammation .
recently , il15rko mice were reported to be hyperphagic and hyperactive , with the suggestion that il-15 may control hypothalamic pathways which regulate energy balance .
however , il-15 expression , trafficking and effects in the cns are an additional , relatively unexplored area of investigation which could impact the balance of energy expenditure and energy intake .
findings from cell culture , laboratory animal , and human studies indicate il-15 regulates adipose tissue deposition by a direct mechanism .
there are conflicting reports concerning the tissue origin of circulating il-15 and whether it can act as a circulating , muscle - derived 
whatever the tissue of origin , recent evidence supports the hypothesis that circulating il-15 levels and il-15 bioactivity are determined by differential association of il-15 with sil-15r variants .
the concordance of basic science findings and human genetic studies suggests the sil-15r , which in turn regulates il-15 , is an important factor influencing body composition and insulin sensitivity .
therefore , further investigation into the complex il-15/il-15r axis is needed to determine if this system can be exploited for regulation of adiposity .
 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-15r ) 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-15r may be novel targets for pharmacologic control of obesity in the human population . 
1. Introduction
2. Molecular Genetics and Expression of IL-15 with Regard to Adipose Tissue
3. Effects of Interleukin-15 on Adipose Tissue
4. IL-15 as a Potential Myokine
5. The Soluble IL-15 Receptor-Alpha as a Modulator of IL-15 Secretion
6. Effects of IL-15 via the Central Nervous System (CNS)
7. Conclusions