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. mesenchymal stem cells ͉ obesity ͉ therapeutics ͉ diabetes ͉ vibration

The age-induced decline in the body's ability to fight disease is exacerbated by obesity and metabolic disease. Using a mouse model of diet-induced obesity, the combined challenge of a high-fat diet and age on liver morphology and biochemistry was characterized, while evaluating the potential of 15 min per day of high frequency (90 Hz), extremely low-magnitude (0.2 G) mechanical signals (LMMS) to suppress lipid accumulation in the liver. Following a 36-week protocol (animals 43 weeks of age), suppression of hepatomegaly and steatosis was reflected by a 29% lower liver mass in LMMS animals as compared with controls. Average triglyceride content was 101.7±19.4 mg mg À1 tissue in the livers of high-fat diet control (HFD) animals, whereas HFD þ LMMS animals realized a 27% reduction to 73.8 ± 22.8 mg mg À1 tissue. In HFD þ LMMS animals, liver free fatty acids were also reduced to 0.026±0.009 mEq mg À1 tissue from 0.035±0.005 mEq mg À1 tissue in HFD. Moderate to severe micro-and macrovesicular steatosis in HFD was contrasted to a 49% reduction in area covered by the vacuoles of at least 15 mm 2 in size in HFD þ LMMS animals. These data provide preliminary evidence of the ability of LMMS to attenuate the progression of fatty liver disease, most likely achieved indirectly by suppressing adipogenesis and thus the total adipose burden through life, thereby reducing a downstream challenge to liver morphology and function. Keywords: diet-induced obesity; aging; liver steatosis; mechanical loading; triglycerides; free fatty acids Nonalcoholic fatty liver disease (NAFLD) is a common disorder associated with excess adiposity, occurring in 10-15% of normal-weight individuals but afflicting up to 80% of the obese. 1 Evidence indicates that this disease is the hepatic component of the obesity-induced metabolic syndrome, with gradual weight loss recognized as the principal therapeutic strategy to slow its progression. An increase in NAFLD has paralleled the rising incidence of obesity, with statistics from 1986 to 1988 showing that 25.5% of hospitalizations with a discharge diagnosis of NAFLD had a concurrent diagnosis of obesity, compared with 43.3% over the period of 2004-2006. Recent reports indicate that low-magnitude mechanical signals (LMMS) suppress adiposity 2 and diet-induced obesity (DIO) 3 by inhibiting adipogenesis in a young adult mouse. LMMS is a high-frequency (30-90 Hz), extremely lowmagnitude mechanical signal, with the 12 m displacement of the oscillating platform barely perceptible to human touch. After 6 weeks, LMMS increased the number of bone marrow-derived stem cells, and after 12 weeks a marked reduction in visceral and total body adiposity was measured. It was hypothesized that organs compromised by lipid accumulation would therefore be protected by these mechanical signals. In this study, using a high-fat diet mouse model of DIO, we investigate the ability of LMMS to protect against several indices of NAFLD.