title: Interleukin-15 contributes to the regulation of murine adipose tissue and human adipocytes.
abstract: An alarming global rise in the prevalence of obesity and its contribution to the development of chronic diseases is a serious health concern. Recently, obesity has been described as a chronic low-grade inflammatory condition, influenced by both adipose tissue and immune cells suggesting proinflammatory cytokines may play a role in its etiology. Here we examined the effects of interleukin-15 (IL-15) on adipose tissue and its association with obesity. Over expression of IL-15 (IL-15tg) was associated with lean body condition whereas lack of IL-15 (IL-15(-/-)) results in significant increase in weight gain without altering appetite. Interestingly, there were no differences in proinflammatory cytokines such as IL-6 and tumor necrosis factor-alpha (TNF-alpha) in serum between the three strains of mice. In addition, there were significant numbers of natural killer (NK) cells in fat tissues from IL-15tg and B6 compared to IL-15(-/-) mice. IL-15 treatment results in significant weight loss in IL-15(-/-) knockout and diet-induced obese mice independent of food intake. Fat pad cross-sections show decreased pad size with over expression of IL-15 is due to adipocyte shrinkage. IL-15 induces weight loss without altering food consumption by affecting lipid deposition in adipocytes. Treatment of differentiated human adipocytes with recombinant human IL-15 protein resulted in decreased lipid deposition. In addition, obese patients had significantly lower serum IL-15 levels when compared to normal weight individuals. These results clearly suggest that IL-15 may be involved in adipose tissue regulation and linked to obesity.
authors.affiliation: Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Barra
authors.forename: Sarah
authors.initials: S
authors.lastname: Reid
authors.forename: Randy
authors.initials: R
authors.lastname: MacKenzie
authors.forename: Geoff
authors.initials: G
authors.lastname: Werstuck
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Trigatti
authors.forename: Carl
authors.initials: C
authors.lastname: Richards
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001066:Appetite; D016207:Cytokines / Q000097:blood; D002149:Energy Intake; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D019409:Interleukin-15 / Q000097:blood / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins; D015430:Weight Gain / Q000502:physiology*; D015431:Weight Loss / Q000502:physiology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D019409:Interleukin-15; D011994:Recombinant Proteins