Development of diet-induced fatty liver disease in the aging mouse is suppressed by brief daily exposure to low-magnitude mechanical signals

Abstract

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 μg mg⁻¹ tissue in the livers of high-fat diet control (HFD) animals, whereas HFD+LMMS animals realized a 27% reduction to 73.8±22.8 μg mg⁻¹ tissue. In HFD+LMMS animals, liver free fatty acids were also reduced to 0.026±0.009 μEq mg⁻¹ tissue from 0.035±0.005 μEq mg⁻¹ 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 μm² in size in HFD+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.