Hyocholic acid retards renal fibrosis by regulating lipid metabolism and inflammatory response in a sheep model

Abstract

The kidneys are vital organs that regulate metabolic homeostasis in the body, filter waste products from the blood, and remove extrahepatic bile acids. We previously found that the dietary supplementation of hyocholic acid alleviated the sheep body lipid deposition and decreased kidney weight. This study evaluated hyocholic acid’s (HCA) roles and mechanisms on lipid metabolism and anti-inflammatory function in the kidney under a high-energy diet. Histomicrograph showing the apparent improvement by HCA by attenuating structural damage. The HCA treatment reduced the renal accumulation of cholesterol. Bile acid receptors such as LXR and FXR were activated at the protein level. HCA significantly altered several genes related to immune response (NF-κB, IL-6, and MCP1) and fibrosis (TGF-β, Col1α1, and α-SMA). These significant changes correlated with renal lipid accumulation. The KEGG pathways including non-alcoholic fatty liver disease, insulin resistance, TNF signaling pathway, and Th17 cell differentiation were enriched and NF-κB, IL-6, and TGF-β were identified as the core interconnected genes. This study revealed that HCA plays an efficient role in alleviating kidney lipids accumulation and inflammatory response through crucial genes such as FXR, LXR, HMGCR, NF-κB, IL-6, MCP1, and TGF-β, and expand our understanding of HCA's role in kidney function. In conclusion, HCA mitigated kidney fibrosis, lipid metabolism disorders and immune responses induced by a high-energy diet by regulating a potential LXR/SREBP2/TGF-β-NF-κB signaling pathway.