Rubin C T, Capilla E, Luu Y K, Busa B, Crawford H, Nolan D J, Mittal V, Rosen C J, Pessin J E, Judex S
Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17879-84. doi: 10.1073/pnas.0708467104. Epub 2007 Oct 24.
Obesity, a global pandemic that debilitates millions of people and burdens society with tens of billions of dollars in health care costs, is deterred by exercise. Although it is presumed that the more strenuous a physical challenge the more effective it will be in the suppression of adiposity, here it is shown that 15 weeks of brief, daily exposure to high-frequency mechanical signals, induced at a magnitude well below that which would arise during walking, inhibited adipogenesis by 27% in C57BL/6J mice. The mechanical signal also reduced key risk factors in the onset of type II diabetes, nonesterified free fatty acid and triglyceride content in the liver, by 43% and 39%, respectively. Over 9 weeks, these same signals suppressed fat production by 22% in the C3H.B6-6T congenic mouse strain that exhibits accelerated age-related changes in body composition. In an effort to understand the means by which fat production was inhibited, irradiated mice receiving bone marrow transplants from heterozygous GFP+ mice revealed that 6 weeks of these low-magnitude mechanical signals reduced the commitment of mesenchymal stem cell differentiation into adipocytes by 19%, indicating that formation of adipose tissue in these models was deterred by a marked reduction in stem cell adipogenesis. Translated to the human, this may represent the basis for the nonpharmacologic prevention of obesity and its sequelae, achieved through developmental, rather than metabolic, pathways.
肥胖是一种全球性流行病,使数百万人身体衰弱,并给社会带来高达数百亿美元的医疗保健成本负担,而运动可抑制肥胖。虽然一般认为身体挑战越剧烈,对抑制肥胖就越有效,但本文表明,在C57BL/6J小鼠中,每天短暂暴露于高频机械信号15周,其强度远低于行走时产生的强度,可使脂肪生成减少27%。该机械信号还分别使II型糖尿病发病的关键风险因素——肝脏中的非酯化游离脂肪酸和甘油三酯含量降低了43%和39%。在9周时间里,同样的信号使表现出与年龄相关的身体成分加速变化的C3H.B6-6T同源小鼠品系的脂肪生成减少了22%。为了了解抑制脂肪生成的方式,接受来自杂合GFP+小鼠骨髓移植的辐照小鼠显示,6周的这些低强度机械信号使间充质干细胞向脂肪细胞分化的比例降低了19%,这表明在这些模型中脂肪组织的形成受到干细胞脂肪生成显著减少的抑制。对人类而言,这可能代表了通过发育途径而非代谢途径实现肥胖及其后遗症非药物预防的基础。