Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues.
OBJECTIVE
IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues.


METHODS
Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells.


RESULTS
Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues.


CONCLUSIONS
Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.
Division of Immunology, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Gregory
G
Lacraz
Division of Immunology, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Volatiana
V
Rakotoarivelo
Institut Universitaire de Cardiologie et de Pneumologie, Québec City, Québec, Canada.
Sebastien M
SM
Labbé
Department of Biochemistry, University of Montréal, Montreal, Québec, Canada.
Mathieu
M
Vernier
Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Christophe
C
Noll
Division of Immunology, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Marian
M
Mayhue
Division of Immunology, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Jana
J
Stankova
Department of Cardiology, McGill University, Montreal, Québec, Canada.
Adel
A
Schwertani
Department of Surgery, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Guillaume
G
Grenier
Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
André
A
Carpentier
Institut Universitaire de Cardiologie et de Pneumologie, Québec City, Québec, Canada.
Denis
D
Richard
Department of Biochemistry, University of Montréal, Montreal, Québec, Canada.
Gerardo
G
Ferbeyre
Department of Surgery, Laval University, CRCHU de Québec-Université Laval, Québec, Canada.
Julie
J
Fradette
Division of Immunology, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Marek
M
Rola-Pleszczynski
Department of Microbiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Alfredo
A
Menendez
Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Marie-France
MF
Langlois
Division of Immunology, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Subburaj
S
Ilangumaran
Division of Immunology, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, CRCHUS, Sherbrooke, Québec, Canada.
Sheela
S
Ramanathan
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