Expression of 738 genes and 52 miRNAs were Chenodeoxycholic Acid dependently decreased, whereas 1566 genes and 29 miRNAs were significantly increased in hepatocytes. Distinct gene clusters controlling BA and lipid homeostasis (FGF(R), APO and FABP family members, HMGCS2) and drug metabolism (CYP, UGT and SULT family members) were significantly modulated by CDCA. Importantly, CDCA affected distinct microRNAs, including miR-34a, -505, -885, -1260 and -552 that systematically correlated in expression with gene clusters responsible for bile acid, lipid and drug homeostasis incorporating genes, such as e.g. SLCO1B1, SLC22A7, FGF19, CYP2E1, CYP1A2, APO family members and FOXO3.
The main methods: Five batches of primary human hepatocytes were treated with 50 μmol/L chenodeoxycholic acid (CDCA) for 24 or 48 h. Total RNA was extracted, size fractionated and subjected to Next Generation Sequencing to generate mRNA and miRNA profiles. The Aims: Bile acids (BAs) are important gut signaling hormones, influencing lipid, glucose, and energy homeostasis. The exact mechanisms behind these effects are not yet fully understood. Lately, they have come to the fore as putative therapeutics in metabolic diseases, such as e.g. nonalcoholic fatty liver disease (NAFLD). We elucidate to what extent BAs impacts on the mRNAome and microRNAome in hepatocytes to gather novel insights into the mechanisms behind metabolic and toxicologic effects of bile acids.
Hepatitis B can cause abnormal liver function, which must be resolved in order to antiviral treatment, not much sense to use these drugs ursodeoxycholic acid or Chenodeoxycholic Acid, which is not suitable for the treatment of hepatitis B. Pure bile acids to reduce is not much use.