Oversecretion of interleukin-15 from skeletal muscle reduces adiposity
Oversecretion of interleukin-15 from skeletal muscle reduces adiposity
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DOI：
10.1152/ajpendo.90506.2008
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发表时间：
2009-01-01
影响因子：
5.1
通讯作者：
Argiles, Josep M.
中科院分区：
文献类型：
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作者：
Quinn, LeBris S.;Anderson, Barbara G.;Argiles, Josep M.
Quinn LS、Anderson BG、Strait-Bodey L、Stroud AM、Argiles JM。骨骼肌过度分泌白细胞介素 15 可减少肥胖。 Am J Physiol Endocrinol Metab 296：E191-E202，2009。首次发表于 2008 年 11 月 11 日； doi: 10.1152/ajpendo.90506.2008.-肥胖是胰岛素抵抗、2 型糖尿病、心血管疾病、骨关节炎和某些癌症的危险因素。过量脂肪沉积的许多不良健康后果是由脂肪组织促炎性脂肪因子分泌增加引起的。肌肉与脂肪的相互信号传导因子或肌因子已开始被识别。白细胞介素-15 (IL-15) 是一种在肌肉组织中高表达的细胞因子，根据细胞培养实验，已提出其作为循环肌因子抑制脂肪组织沉积。为了在体内验证这一假设，构建了两个在骨骼肌组织中过度表达 IL-15 mRNA 和蛋白质的转基因小鼠品系。通过用更有效的信号肽替代低效的天然 IL-15 信号肽，其中一种转基因小鼠系也表现出循环中 IL-15 分泌增加。 IL-15 在肌肉组织中过度表达而不分泌到血流中导致身体成分没有差异。 IL-15循环水平的升高导致体脂显着减少和骨矿物质含量增加，而不会明显影响去脂体重或其他细胞因子的水平。 IL-15 循环水平的升高还可以抑制雄性转基因小鼠因摄入高脂肪/高能量饮食而引起的肥胖，但对雌性转基因小鼠则不然。血清 IL-15 升高的雌性小鼠在低脂肪/低能量饮食和高脂肪/高能量饮食中表现出瘦体重沉积增加。这些发现表明，肌肉来源的循环 IL-15 可以调节脂肪组织沉积，并支持将 IL-15 添加到越来越多地参与身体成分调节的潜在肌因子列表中。
Quinn LS, Anderson BG, Strait-Bodey L, Stroud AM, Argiles JM. Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am J Physiol Endocrinol Metab 296: E191-E202, 2009. First published November 11, 2008; doi: 10.1152/ajpendo.90506.2008.-Obesity is a risk factor for development of insulin resistance, type 2 diabetes, cardiovascular disease, osteoarthritis, and some forms of cancer. Many of the adverse health consequences of excess fat deposition are caused by increased secretion of proinflammatory adipokines by adipose tissue. Reciprocal muscle-to-fat signaling factors, or myokines, are starting to be identified. Interleukin-15 (IL-15) is a cytokine that is highly expressed in muscle tissue and that, on the basis of cell culture experiments, has been proposed to act as a circulating myokine that inhibits adipose tissue deposition. To test this hypothesis in vivo, two lines of transgenic mice that overexpressed IL-15 mRNA and protein in skeletal muscle tissue were constructed. By substitution of the inefficient native IL-15 signal peptide with a more efficient signal peptide, one of the transgenic mouse lines also exhibited elevated secretion of IL-15 in the circulation. Overexpression of IL-15 in muscle tissue without secretion in the bloodstream resulted in no differences in body composition. Elevated circulating levels of IL-15 resulted in significant reductions in body fat and increased bone mineral content, without appreciably affecting lean body mass or levels of other cytokines. Elevated circulating levels of IL-15 also inhibited adiposity induced by consumption of a high-fat/high-energy diet in male, but not female, transgenic mice. Female mice with elevated serum IL-15 exhibited increased deposition of lean body mass on a low-fat/low-energy diet and a high-fat/high-energy diet. These findings indicate that muscle-derived circulating IL-15 can modulate adipose tissue deposition and support addition of IL-15 to the growing list of potential myokines that are increasingly being implicated in regulation of body composition.