Interleukin-15 modulates adipose tissue by altering mitochondrial mass and activity.

Interleukin-15 modulates adipose tissue by altering mitochondrial mass and activity.
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DOI:
10.1371/journal.pone.0114799
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Ashkar AA
Ashkar AA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Barra NG;Palanivel R;Denou E;Chew MV;Gillgrass A;Walker TD;Kong J;Richards CD;Jordana M;Collins SM;Trigatti BL;Holloway AC;Raha S;Steinberg GR;Ashkar AA

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白细胞介素-15(IL-15)是一种免疫调节细胞因子,可独立于淋巴细胞影响体重调节;然而,涉及的潜在机制仍不清楚。为了研究这些机制,我们进行了代谢笼研究,评估了肠道细菌多样性和大量营养素吸收,并检查了培养的脂肪细胞和瘦IL-15转基因(IL-15 tg),超重IL-15缺陷(IL-15−/−)和对照C57 Bl/6(B6)小鼠中的脂肪线粒体活性。在这里,我们表明,体重的差异不是不同的活动水平,食物摄入量或呼吸交换率的结果。虽然已知肥胖和瘦个体之间的肠道微生物群差异会影响大量营养素吸收,但这些鼠品系中不同的肠道细菌谱并不转化为定殖无菌动物的体重差异和大量营养素吸收。由于其对体重变化的贡献,我们检查了线粒体因子,发现IL-15处理培养的脂肪细胞导致线粒体膜电位增加和脂质沉积减少。最后,与B6和IL-15−/−小鼠相比,IL-15 tg小鼠脂肪组织中的线粒体活性和质量显著升高。总之,这些结果表明,IL-15参与脂肪组织调节,并与线粒体功能改变有关。
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.
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