Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre and Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
PLoS One. 2012;7(6):e39553. doi: 10.1371/journal.pone.0039553. Epub 2012 Jun 29.
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.
肥胖是一种慢性炎症状态，其特征是促炎免疫细胞的激活和浸润，以及促炎细胞因子的失调产生。虽然白细胞介素-15（IL-15）已知是免疫自然杀伤（NK）细胞功能和发育的关键调节剂，但我们最近证明，在小鼠和人类中，IL-15 的表达减少与体重增加和肥胖密切相关。以前，我们和其他人已经表明，肥胖个体的循环 IL-15 和 NK 细胞水平较低。与野生型和 NK 细胞缺陷肥胖 IL-15(-/-)小鼠相比，瘦素 IL-15 过表达（IL-15 tg）小鼠的脂肪 NK 细胞积累增加。由于 IL-15 可诱导 IL-15(-/-)和饮食诱导肥胖小鼠体重减轻，并对各种淋巴细胞产生影响，本文旨在确定淋巴细胞，特别是 NK 细胞，是否在 IL-15 介导的体重减轻中发挥作用。急性 IL-15 处理导致 B6 小鼠脂肪组织中 NK、NKT 和 CD3(+) T 细胞的积累增加。NK 和 NKT 细胞耗竭的小鼠与用 IL-15 治疗的对照组相比，体重减轻相似。最后，IL-15 治疗可诱导淋巴细胞缺陷 RAG2(-/-)γc(-/-)小鼠显著体重减轻，与食物摄入无关。脂肪垫切片显示，细胞因子治疗后垫大小减小是由于脂肪细胞收缩。这些结果清楚地表明，IL-15 介导的体重减轻与淋巴细胞无关。
