Patel Vihitaben S, Chan M Ete, Pagnotti Gabriel M, Frechette Danielle M, Rubin Janet, Rubin Clinton T
Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA.
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Obesity (Silver Spring). 2017 Oct;25(10):1745-1753. doi: 10.1002/oby.21958. Epub 2017 Aug 25.
The aim of this study was to determine whether inclusion of a refractory period between bouts of low-magnitude mechanical stimulation (LMMS) can curb obesity-induced adipose tissue dysfunction and sequelae in adult mice.
A diet-induced obesity model that included a diet with 45% of kilocalories from fat was employed with intention to treat. C57BL/6J mice were weight matched into four groups: low-fat diet (LFD, n = 8), high-fat diet (HFD, n = 8), HFD with one bout of 30-minute LMMS (HFDv, n = 9), and HFD with two bouts of 15-minute LMMS with a 5-hour separation (refractory period, RHFDv, n = 9). Two weeks of diet was followed by 6 weeks of diet plus LMMS.
HFD and HFDv mice continued gaining body weight and visceral adiposity throughout the experiment, which was mitigated in RHFDv mice. Compared with LFD mice, HFD and HFDv mice had increased rates of adipocyte hypertrophy, increased immune cell infiltration (B cells, T cells, and macrophages) into adipose tissue, increased adipose tissue inflammation (tumor necrosis factor alpha gene expression), and a decreased proportion of mesenchymal stem cells in adipose tissue, all of which were rescued in RHFDv mice. Glucose intolerance and insulin resistance were elevated in HFD and HFDv mice, but not in RHFDv mice, as compared with LFD mice.
Incorporating a 5-hour refractory period between bouts of LMMS attenuates obesity-induced adipose tissue dysfunction and improves glucose metabolism.
本研究旨在确定在低强度机械刺激（LMMS）疗程之间设置不应期是否可以抑制成年小鼠肥胖诱导的脂肪组织功能障碍及后遗症。
采用饮食诱导肥胖模型，所用饮食含45%的千卡热量来自脂肪，用于治疗目的。将C57BL/6J小鼠按体重匹配分为四组：低脂饮食组（LFD，n = 8）、高脂饮食组（HFD，n = 8）、接受一轮30分钟LMMS的高脂饮食组（HFDv，n = 9）和接受两轮间隔5小时（不应期）的15分钟LMMS的高脂饮食组（RHFDv，n = 9）。两周饮食期后进行为期6周的饮食加LMMS干预。
在整个实验过程中，HFD和HFDv组小鼠体重和内脏脂肪持续增加，而RHFDv组小鼠这种情况得到缓解。与LFD组小鼠相比，HFD和HFDv组小鼠的脂肪细胞肥大率增加、免疫细胞（B细胞、T细胞和巨噬细胞）向脂肪组织的浸润增加、脂肪组织炎症（肿瘤坏死因子α基因表达）增加以及脂肪组织中间充质干细胞比例降低，所有这些在RHFDv组小鼠中均得到改善。与LFD组小鼠相比，HFD和HFDv组小鼠的葡萄糖不耐受和胰岛素抵抗升高，但RHFDv组小鼠未出现这种情况。
在LMMS疗程之间设置5小时的不应期可减轻肥胖诱导的脂肪组织功能障碍并改善葡萄糖代谢。
