604-P: Different Exercise Exposures May Protect against Developmental Programming of MASLD in Male Mice?

Introduction: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is a chronic liver disease that affects up to a fourth of the adults in the US. Maternal obesogenic diet exposure (MODE) programs worse MASLD in offspring. The beneficial effects of exercise on metabolic disease are well defined. We hypothesized that offspring exercise would mitigate the developmental programming effects of MODE.

Methods: To determine the effect of offspring exercise, male offspring from dams fed chow or High Fat Fructose and Cholesterol (HFFC) diet underwent voluntary exercise. The three exercise conditions include voluntary exercise on a wheel for 3 weeks before (pre exercise) feeding a MASLD-inducing diet, exercise from 3 weeks before and during MASLD-diet feeding (continuous exercise) and sedentary conditions. Body weight and liver weights were measured. Histologic analysis and qPCR was performed to assess disease severity.

Results: Exercise before and during HFFC feeding decreased body weight and liver weight to body weight ratio. Preliminary results show a reduction in steatosis and inflammation in offspring with continued exercise during HFFC feeding. Both pre-exercise alone and continued exercise during HFFC feeding show a trend toward attenuating the increase in fibrosis observed in MODE offspring.

Conclusion: Preliminary data support that exercise may attenuate developmentally programmed worsening of MASLD by MODE. Continual exercise appears to have a greater benefit than pre-exercise alone.