title: Interleukin-15 modulates adipose tissue by altering mitochondrial mass and activity.
abstract: Interleukin-15 (IL-15) is an immunomodulatory cytokine that affects body mass regulation independent of lymphocytes; however, the underlying mechanism(s) involved remains unknown. In an effort to investigate these mechanisms, we performed metabolic cage studies, assessed intestinal bacterial diversity and macronutrient absorption, and examined adipose mitochondrial activity in cultured adipocytes and in lean IL-15 transgenic (IL-15tg), overweight IL-15 deficient (IL-15-/-), and control C57Bl/6 (B6) mice. Here we show that differences in body weight are not the result of differential activity level, food intake, or respiratory exchange ratio. Although intestinal microbiota differences between obese and lean individuals are known to impact macronutrient absorption, differing gut bacteria profiles in these murine strains does not translate to differences in body weight in colonized germ free animals and macronutrient absorption. Due to its contribution to body weight variation, we examined mitochondrial factors and found that IL-15 treatment in cultured adipocytes resulted in increased mitochondrial membrane potential and decreased lipid deposition. Lastly, IL-15tg mice have significantly elevated mitochondrial activity and mass in adipose tissue compared to B6 and IL-15-/- mice. Altogether, these results suggest that IL-15 is involved in adipose tissue regulation and linked to altered mitochondrial function.
authors.affiliation: Department of Pathology and Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada; Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Barra
authors.affiliation: Department of Medicine and Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Rengasamy
authors.initials: R
authors.lastname: Palanivel
authors.affiliation: Department of Medicine and Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada; Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Denou
authors.affiliation: Department of Pathology and Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada; Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Marianne V
authors.initials: MV
authors.lastname: Chew
authors.affiliation: Department of Pathology and Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada; Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Gillgrass
authors.affiliation: Department of Pathology and Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Tina D
authors.initials: TD
authors.lastname: Walker
authors.affiliation: Department of Pathology and Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Josh
authors.initials: J
authors.lastname: Kong
authors.affiliation: Department of Pathology and Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Carl D
authors.initials: CD
authors.lastname: Richards
authors.affiliation: Department of Pathology and Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.affiliation: Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Collins
authors.affiliation: Department of Biochemistry and Biomedical Sciences and Atherothrombosis Research Group, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Bernardo L
authors.initials: BL
authors.lastname: Trigatti
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Raha
authors.affiliation: Department of Medicine and Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Steinberg
authors.affiliation: Department of Pathology and Molecular Medicine and McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada; Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001835:Body Weight; D018925:Chemokines / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D019409:Interleukin-15 / Q000172:deficiency / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis; D007422:Intestines / Q000382:microbiology; D008297:Male; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008822:Mice, Transgenic; D064307:Microbiota; D008928:Mitochondria / Q000378:metabolism*; D053142:Mitochondrial Size; D050177:Overweight / Q000378:metabolism / Q000473:pathology
chemical_list: D018925:Chemokines; D019409:Interleukin-15; D015850:Interleukin-6; C074302:keratinocyte-derived chemokines