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Communicated by William J. Lennarz, Stony Brook University, Stony Brook, NY, September 19, 2007 (received for review June 20, 2007)
Abstract
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.
Footnotes
- †To whom correspondence should be addressed. E-mail: clinton.rubin{at}sunysb.edu
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Author contributions: C.T.R., C.J.R., J.E.P., and S.J. designed research; C.T.R., E.C., Y.K.L., B.B., J.E.P., and S.J. performed research; H.C., D.J.N., V.M., and C.J.R. contributed new reagents/analytic tools; C.T.R., E.C., Y.K.L., B.B., J.E.P., and S.J. analyzed data; and C.T.R. wrote the paper.
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Conflict of interest statement: C.T.R. is a founder of and consultant for Juvent Medical, Inc. C.T.R., S.J., and J.E.P. have submitted a provisional patent to the U.S. Patent and Trademark Office regarding the method and application of the technology.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0708467104/DC1.
- Abbreviations:
- LMMS,
- low-magnitude mechanical signal;
- CTR,
- control;
- FFA,
- free fatty acid;
- NEFA,
- nonesterified FFA;
- TG,
- triglyceride;
- MSC,
- mesenchymal stem cell.
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Freely available online through the PNAS open access option.
- © 2007 by The National Academy of Sciences of the USA
Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals
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