Inhibition of the Primary Bile Acid Synthesis Pathways in SD Rats at Different Altitudes

Bile acids, the primary constituents of mammalian bile, are synthesized in the liver from cholesterol and secreted into the intestine to perform essential physiological functions. Primary bile acid synthesis is the principal pathway for cholesterol catabolism and whole-body cholesterol homeostasis, occurring predominantly via the classical and alternative pathways. To elucidate the effects of altitude on serum bile acid profiles and synthesis pathways in SD rats, this study utilized UPLC-MS/MS to analyze serum bile acid composition in animals housed at high and low altitudes. Additionally, qRT-PCR and Western blotting assessed mRNA transcription and protein expression of key genes involved in primary bile acid synthesis in the liver and intestinal tissues (ileum, duodenum, and colon). Results showed that serum levels of total and primary bile acids significantly decreased with increasing altitude. Furthermore, hepatic mRNA and protein expression of Cyp7a1, Cyp8b1, Cyp27a1, and Cyp7b1 were significantly downregulated. Fxr mRNA expression in the liver, ileum, duodenum, and colon was significantly decreased with increasing altitude. Meanwhile, the protein expression of both FGF15 and SHP showed a downward trend, with a significant decrease for FGF15 and a non-significant decrease for SHP. These findings suggest that primary bile acid synthesis in SD rats is dominated by the classical pathway. As altitude increases, bile acid synthesis in SD rats is significantly inhibited, indicating that high-altitude hypobaric hypoxia is the primary inhibitory factor. This study provides critical data for elucidating the adaptive mechanisms of bile acid metabolism in mammals exposed to high-altitude hypoxia, thereby establishing a theoretical foundation for investigating the regulation of host lipid metabolism influenced by such conditions.