Kugler Benjamin A, Maurer Adrianna, Fu Xiaorong, Franczak Edziu, Ernst Nick, Schwartze Kevin, Allen Julie, Li Tiangang, Crawford Peter A, Koch Lauren G, Britton Steven L, Burgess Shawn C, Thyfault John P
Departments of Cell Biology and Physiology.
Internal Medicine, Division of Endocrinology and Clinical Pharmacology and KU Diabetes Institute.
bioRxiv. 2024 Oct 24:2024.10.21.619494. doi: 10.1101/2024.10.21.619494.
High cardiorespiratory fitness and exercise show evidence of altering bile acid (BA) metabolism and are known to protect or treat diet-induced hepatic steatosis, respectively. Here, we tested the hypothesis that high intrinsic aerobic capacity and exercise both increase hepatic BA synthesis measured by the incorporation of HO. We also leveraged mice with inducible liver-specific deletion of (LCyp7a1KO), which encodes the rate-limiting enzyme for BA synthesis, to test if exercise-induced BA synthesis is critical for exercise to reduce hepatic steatosis. The synthesis of hepatic BA, cholesterol, and lipogenesis was measured in rats bred for either high (HCR) vs. low (LCR) aerobic capacity consuming acute and chronic high-fat diets. HCR rats had increased synthesis of cholesterol and certain BA species in the liver compared to LCR rats. We also found that chronic exercise with voluntary wheel running (VWR) (4 weeks) increased newly synthesized BAs of specific species in male C57BL/6J mice compared to sedentary mice. Loss of resulted in fewer new BAs and increased liver triglycerides compared to controls after a 10-week high-fat diet. Additionally, exercise via VWR for 4 weeks effectively reduced hepatic triglycerides in the high-fat diet-fed control male and female mice as expected; however, exercise in LCyp7a1KO mice did not lower liver triglycerides in either sex. These results show that aerobic capacity and exercise increase hepatic BA metabolism, which may be critical for combatting hepatic steatosis.
高心肺适能和运动显示出改变胆汁酸（BA）代谢的证据，并且已知分别对饮食诱导的肝脂肪变性具有保护或治疗作用。在此，我们检验了以下假设：高内在有氧能力和运动均会增加通过HO掺入法测定的肝脏BA合成。我们还利用可诱导肝脏特异性缺失（LCyp7a1KO）的小鼠，该基因编码BA合成的限速酶，以测试运动诱导的BA合成对于运动减轻肝脂肪变性是否至关重要。在食用急性和慢性高脂饮食的高（HCR）与低（LCR）有氧能力品系的大鼠中，测量肝脏BA、胆固醇和脂肪生成的合成。与LCR大鼠相比，HCR大鼠肝脏中的胆固醇和某些BA种类的合成增加。我们还发现，与久坐的小鼠相比，雄性C57BL/6J小鼠通过自愿轮跑（VWR）进行4周的慢性运动增加了特定种类新合成的BA。在10周高脂饮食后，与对照组相比，LCyp7a1缺失导致新生成的BA减少且肝脏甘油三酯增加。此外，正如预期的那样，通过VWR进行4周运动有效地降低了高脂饮食喂养的对照雄性和雌性小鼠的肝脏甘油三酯；然而，LCyp7a1KO小鼠的运动并未降低任一性别的肝脏甘油三酯。这些结果表明，有氧能力和运动可增加肝脏BA代谢，这可能对对抗肝脂肪变性至关重要。
