Voluntary physical activity in early life attenuates markers of fatty liver disease in adult male rats fed a high-fat diet

Paediatric fatty liver disease (FLD) can develop into steatohepatitis, cirrhosis and hepatocellular carcinoma in adulthood. We assessed if early life physical exercise reduced the effects of high-fat (HF) diet-induced steatosis. Male HF-fed rats with access to a running wheel from weaning until day (D)60 (early exercise) or from D67 to D120 (late exercise) were compared with control HF- or chow-fed groups with no wheel. At D63 and D120, liver histopathology (Kleiner score), type I collagen and plasma enzymes were assessed. At D63, early life activity significantly reduced histopathology scores (total, portal inflammation, steatosis, ballooning, but not lobular inflammation or fibrosis) and the number of rats affected. At D120, HF control scores were higher than in chow-fed controls, but the effect of activity was selective: early exercise reduced portal inflammation, steatosis, ballooning and fibrosis, but late activity affected only portal inflammation and ballooning. The chow-fed portal inflammation score was significantly less than all HF groups, but lobular inflammation was lower in the HF control group only. The fibrosis score in the HF early exercise and control chow group were lower than in the late exercise and sedentary HF groups, indicating that early life exercise was more effective than when activity was introduced later in life. Plasma biomarkers showed minor between-group differences. The retained effect on liver histopathology rat at D120 after only early life exposure activity suggests that timing of introduction of exercise is critical in reducing FLD scores and prevalence in children, young adults and possibly into adulthood.