Lithocholic Acid Improves Metabolic Stress in Caenorhabditis elegans by Reducing Fat Accumulation

A high-salt and high-sugar (HS) diet is a major contributor to metabolic disorders, including lipid accumulation and oxidative stress. Lithocholic acid (LCA), as a key secondary bile acid, plays a crucial role in regulating metabolism and delaying aging. However, the specific molecular mechanisms underlying LCA’s protective effects against HS-induced metabolic damage remain unclear. In this study, using Caenorhabditis elegans as a model organism, we systematically investigated the protective effects of different concentrations of LCA against HS-induced metabolic damage and their regulatory mechanisms through lifespan analysis, oxidative stress phenotype testing, mitochondrial function assessment, intestinal barrier integrity evaluation, and molecular pathway validation. The aim was to explore the benefits of LCA against HS-induced metabolic abnormalities and to elucidate its potential molecular mechanisms. Result: In HS model, LCA treatment significantly improves overall health in nematodes, enhances motility, and extends lifespan. LCA effectively boosts antioxidant stress resistance in HS conditions, reduces reactive oxygen species (ROS) accumulation, positively regulates mitochondrial membrane potential to maintain stable mitochondrial function, and activates the AMPK signaling pathway. Furthermore, LCA mitigates HS-induced intestinal barrier damage, reduces intestinal permeability, and preserves gut structure and homeostasis. Concurrently, LCA alleviates HS-induced metabolic dysregulation by regulating the sbp-1/nhr-49 metabolic axis, ultimately exerting systemic protective effects through multiple targets and pathways. Conclusion: LCA may have anti-aging qualities, antioxidant properties and the capacity to raise metabolic levels when exposed to HS.