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Interleukin-15 (IL-15) is a cytokine that is highly expressed in muscle tissue and that, on the basis of cell culture experiments, has been proposed to act as a circulating myokine that inhibits adipose tissue deposition. To test this hypothesis in vivo, two lines of transgenic mice that overexpressed IL-15 mRNA and protein in skeletal muscle tissue were constructed. By substitution of the inefficient native IL-15 signal peptide with a more efficient signal peptide, one of the transgenic mouse lines also exhibited elevated secretion of IL-15 in the circulation. Overexpression of IL-15 in muscle tissue without secretion in the bloodstream resulted in no differences in body composition. Elevated circulating levels of IL-15 resulted in significant reductions in body fat and increased bone mineral content, without appreciably affecting lean body mass or levels of other cytokines. Elevated circulating levels of IL-15 also inhibited adiposity induced by consumption of a high-fat\/high-energy diet in male, but not female, transgenic mice. Female mice with elevated serum IL-15 exhibited increased deposition of lean body mass on a low-fat\/low-energy diet and a high-fat\/high-energy diet. These findings indicate that muscle-derived circulating IL-15 can modulate adipose tissue deposition and support addition of IL-15 to the growing list of potential myokines that are increasingly being implicated in regulation of body composition.<\/jats:p>","DOI":"10.1152\/ajpendo.90506.2008","type":"journal-article","created":{"date-parts":[[2008,11,12]],"date-time":"2008-11-12T01:54:19Z","timestamp":1226454859000},"page":"E191-E202","source":"Crossref","is-referenced-by-count":214,"title":["Oversecretion of interleukin-15 from skeletal muscle reduces adiposity"],"prefix":"10.1152","volume":"296","author":[{"given":"LeBris S.","family":"Quinn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara G.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Strait-Bodey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley M.","family":"Stroud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9p M.","family":"Argil\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01084.2003"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Almendro V, Busquets S, Ametller E, Carb\u00f3 N, Figueras M, Fuster G, Argil\u00e9s JM, L\u00f3pez-Soriano FJ.Effects of interleukin-15 on lipid oxidation. 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