Adipogenesis is inhibited by brief, daily exposure to high-frequency, extremely low-magnitude mechanical signals

C. T. Rubin^*,, E. Capilla, Y. K. Luu^*, B. Busa^*, H. Crawford, D. J. Nolan^,¶, V. Mittal^,¶, C. J. Rosen^||, J. E. Pessin, and S. Judex^*

Departments of *Biomedical Engineering and Pharmacology and ^¶Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724; and ^||The Jackson Laboratory, Bar Harbor, ME 04609

Received for publication 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.

Key Words: mesenchymal stem cells • obesity • therapeutics • diabetes • vibration

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.

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.

This article contains supporting information online at www.pnas.org/cgi/content/full/0708467104/DC1.

To whom correspondence should be addressed. E-mail: clinton.rubin{at}sunysb.edu

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