4.0 Article

Rats with high aerobic capacity display enhanced transcriptional adaptability and upregulation of bile acid metabolism in response to an acute high-fat diet

期刊

PHYSIOLOGICAL REPORTS
卷 10, 期 15, 页码 -

出版社

WILEY
DOI: 10.14814/phy2.15405

关键词

aerobic capacity; bile acids; cholesterol; fatty liver

资金

  1. American Heart Association [14POST20110034]
  2. National Institute of Arthritis and Musculoskeletal and Skin Diseases [5T32AR48523-8]
  3. National Institute of Diabetes and Digestive and Kidney Diseases [DK088940-01A1, F32DK130244, R01DK121497]
  4. NIH [P40OD021331]
  5. VA [01BX003271, 1I01BX002567-05]

向作者/读者索取更多资源

The study found that high aerobic capacity and exercise are associated with upregulation of bile acid synthesis and greater fecal excretion of cholesterol and bile acid, which may contribute to the protection against hepatic steatosis in rodents.
Rats selectively bred for the high intrinsic aerobic capacity runner (HCR) or low aerobic capacity runner (LCR) show pronounced differences in susceptibility for high-fat/high sucrose (HFHS) diet-induced hepatic steatosis and insulin resistance, replicating the protective effect of high aerobic capacity in humans. We have previously shown multiple systemic differences in energy and substrate metabolism that impacts steatosis between HCR and LCR rats. This study aimed to investigate hepatic-specific mechanisms of action via changes in gene transcription. Livers of HCR rats had a greater number of genes that significantly changed in response to 3-day HFHS compared with LCR rats (171 vs. 75 genes: >1.5-fold, p < 0.05). HCR and LCR rats displayed numerous baseline differences in gene expression while on a low-fat control diet (CON). A 3-day HFHS diet resulted in greater expression of genes involved in the conversion of excess acetyl-CoA to cholesterol and bile acid (BA) synthesis compared with the CON diet in HCR, but not LCR rats. These results were associated with higher fecal BA loss and lower serum BA concentrations in HCR rats. Exercise studies in rats and mice also revealed higher hepatic expression of cholesterol and BA synthesis genes. Overall, these results suggest that high aerobic capacity and exercise are associated with upregulated BA synthesis paired with greater fecal excretion of cholesterol and BA, an effect that may play a role in protection against hepatic steatosis in rodents.

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