Endurance exercise training reduces gallstone development in mice.
Gallstones form when the ratio of bile cholesterol to bile acids and phospholipids is elevated, causing cholesterol to precipitate. Physical inactivity is hypothesized to increase gallstone development, but experimental evidence supporting this is lacking, and potential mechanisms for the antilithogenic effects of exercise have not been described. The purpose of this study was to examine the effect of endurance exercise training on gallstone formation and the expression of genes involved in bile cholesterol metabolism in gallstone-sensitive (C57L/J) mice. At 10 wk, 50 male mice began a lithogenic diet and were randomly assigned to an exercise-training (EX) or sedentary (SED) group (n = 25 per group). Mice in the EX group ran on a treadmill at approximately 15 m/min for 45 min/day for 12 wk. At the time animals were euthanized, gallstones were collected, pooled by group, and weighed. The weight of the gallstones was 2.5-fold greater in the SED mice compared with EX mice (143 vs. 57 mg, respectively). In the EX mice, hepatic expression of the low-density lipoprotein receptor (LDLr), scavenger receptor class B type 1 (SRB1), and sterol 27 hydroxylase (Cyp27) was increased by approximately 2-fold (P < 0.05 for each). The LDLr and SRB1 increase cholesterol clearance by low-density lipoprotein and high-density lipoprotein particles, respectively, while Cyp27 promotes the catabolism of cholesterol to bile acids. Taken together, these data indicate that exercise promotes changes in hepatic gene expression that increase cholesterol uptake by the liver but simultaneously increase the catabolism of cholesterol to bile acids, effectively reducing cholesterol saturation in the bile. This suggests a mechanism by which exercise improves cholesterol clearance from the circulation while simultaneously inhibiting gallstone formation.
Wilund
Kenneth R
KR
Department of Kinesiology and Community Health, University of Illinois, 906 S. Goodwin Ave., Urbana, IL 61801, USA. kwilund@uiuc.edu
Feeney
Laura A
LA
Tomayko
Emily J
EJ
Chung
Hae R
HR
Kim
Kijin
K
D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000378:metabolism*; D019826:Cholic Acid / Q000008:administration & dosage / Q000378:metabolism; D004195:Disease Models, Animal; D042882:Gallstones / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D007082:Ileum / Q000201:enzymology / Q000378:metabolism; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010807:Physical Endurance; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
C462601:ABCG8 protein, mouse; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D002791:Cholesterol, Dietary; D008074:Lipoproteins; D012333:RNA, Messenger; D011973:Receptors, LDL; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D006903:Hydroxymethylglutaryl CoA Reductases; D053493:Cholestanetriol 26-Monooxygenase; D019826:Cholic Acid