title: Interleukin-15 treatment induces weight loss independent of lymphocytes.
abstract: Obesity is a chronic inflammatory condition characterized by activation and infiltration of proinflammatory immune cells and a dysregulated production of proinflammatory cytokines. While known as a key regulator of immune natural killer (NK) cell function and development, we have recently demonstrated that reduced expression of the cytokine Interleukin-15 (IL-15) is closely linked with increased body weight and adiposity in mice and humans. Previously, we and others have shown that obese individuals have lower circulating levels of IL-15 and NK cells. Lean IL-15 overexpressing (IL-15 tg) mice had an accumulation in adipose NK cells compared to wildtype and NK cell deficient obese IL-15(-/-) mice. Since IL-15 induces weight loss in IL-15(-/-) and diet induced obese mice and has effects on various lymphocytes, the aim of this paper was to determine if lymphocytes, particularly NK cells, play a role in IL-15 mediated weight loss. Acute IL-15 treatment resulted in an increased accumulation of NK, NKT, and CD3(+) T cells in adipose tissue of B6 mice. Mice depleted of NK and NKT cells had similar weight loss comparable to controls treated with IL-15. Finally, IL-15 treatment induces significant weight loss in lymphocyte deficient RAG2(-/-)γc(-/-) mice independent of food intake. Fat pad cross-sections show decreased pad size with cytokine treatment is due to adipocyte shrinkage. These results clearly suggest that IL-15 mediates weight loss independent of lymphocytes.
authors: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre and Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors: Nicole G
authors: NG
authors: Barra
authors: Marianne V
authors: MV
authors: Chew
authors: Sarah
authors: S
authors: Reid
authors: Ali A
authors: AA
authors: Ashkar
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D000818:Animals; D002452:Cell Count; D048429:Cell Size / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D005260:Female; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency / Q000378:metabolism; D019409:Interleukin-15 / Q000008:administration & dosage / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D017493:Leukocyte Common Antigens / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; C499308:Rag2 protein, mouse; D017493:Leukocyte Common Antigens