Interleukin-15 increases calcineurin expression in 3T3-L1 cells: possible involvement on in vivo adipocyte differentiation.
ABSTRACT Different studies have revealed that the Ca2+-dependent serine/threonine phosphatase calcineurin is involved in the regulation of adipocyte differentiation. Calcineurin acts as a Ca2+-dependent molecular switch that negatively regulates the ability of 3T3-L1 cells to undergo adipocyte differentiation by preventing the expression of critical proadipogenic transcription factors. In this study we investigated the role of interleukin-15 (IL-15), a cytokine previously known to be involved in the control of fat accretion by adipose cells, in the differentiation of the 3T3-L1 preadipose cell line. We found that IL-15 is able to increase alpha-calcineurin mRNA content in white adipose tissue of rats chronically treated with the cytokine and also in the 3T3-L1 preadipose cell line. Moreover, IL-15 promoted a decrease in both leptin mRNA expression and lipid accumulation, as estimated by Red Oil O staining. Cotreatment with IL-15 and FK506 (a calcineurin inhibitor) resulted in no changes in lipid content compared with the non-treated group. These data suggest that IL-15 directly inhibits adipogenesis, possibly by upregulating alpha-calcineurin and preventing the induction of adipocyte differentiation.
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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.PLoS ONE 01/2012; 7(6):e39553. · 3.53 Impact Factor
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ABSTRACT: Interleukin 15 (IL-15) has recently been proposed as a myokine involved in regulating lipid metabolism. We investigated the effect of exercise training on IL-15 content in skeletal muscle and expression of IL-15 receptor (IL-15R) in adipose tissue of obese rats. After 12 weeks of a high-fat diet, obese rats underwent treadmill running at 26 m/min (60 min each, 5 days/week for 8 weeks). High-fat diet induced obesity, with increased body weight, body fat, and lipid profile. The level of IL-15 immunoreactivity (IL-15-ir) in plasma and gastrocnemius muscle was lower in obese than control rats, and the mRNA level of IL-15 in gastrocnemius muscle was markedly decreased. The mRNA and protein levels of IL-15R in adipose tissue were markedly lower in obese rats. Compared with sedentary obese rats, treadmill running showed decreased body weight and elevated mRNA expression of IL-15 in muscle and elevated IL-15-ir level in plasma and muscle. The mRNA and protein level of IL-15R were increased in adipose tissue in treadmill running obese rats. Our results showed that exercise training improve obesity and reversed the downregulation of the IL-15 in muscle and IL-15R in adipose tissue induced by high-fat diet.Endocrine 10/2012; · 3.53 Impact Factor
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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.PLoS ONE 12/2014; 9(12):e114799. · 3.53 Impact Factor