Impact of high fat diet and exercise on bone and bile acid metabolism in rats

Background: Bile acids help facilitate the intestinal lipids absorption, and have endocrine activity in glucose, lipid and bone metabolism. Obesity and exercise influence bile acid metabolism and have opposite effects in bone. This given study investigates if regular exercise helps mitigate the adverse effects of obesity on bone, potentially by reversing alterations in bile acid metabolism. Methods: Four-month-old female Sprague Dawley rats either received high fat diet (HFD) or chow-based standard diet (lean controls). During the 10-month study period, half of the animals performed 30 min of running at moderate speed on five consecutive days followed by two days of rest. The other half was kept inactive (inactive controls). At study end, bone quality was assessed by micro computed tomography and biomechanical testing. Bile acids were measured in serum and stool. Results: HFD feeding was related to reduced trabecular (-33%, p=1.14x10-7) and cortical (-21%, p=2.9x10-8) bone mass, and lowered femoral stiffness (12-41%, p=0.005). Furthermore, HFD decreased total bile acids in serum (-37%, p=1.0x10-6), but increased bile acids in stool (+2-fold, p=7.3x10-9). These quantitative effects were accompanied by changes in the relative abundance of individual bile acids. The concentration of serum bile acids correlated positively with all cortical bone parameters (r=0.593 - 0.708), whilst stool levels showed inverse correlations at cortical (r=-0.651 - -0.805) and trabecular level (r=-0.656 - -0.750). Exercise improved some trabecular and cortical bone quality parameters (+11-31%, p=0.043 to 0.001) in lean controls, but failed to revert the bone loss related to HFD. Similarly, changes in bile acid metabolism were not mitigated by exercise. Conclusion: Prolonged HFD consumption induced quantitative and qualitative alterations in bile acid metabolism, accompanied by bone loss. Tight correlations between bile acids and structural indices of bone quality support further functional analyses on the potential role of bile acids in bone metabolism. Regular moderate exercise improved trabecular and cortical bone quality in lean controls but failed mitigating the effects related to HFD in bone and bile acid metabolism. ### Competing Interest Statement The authors have declared no competing interest.