As the metabolic hub of the human body, the liver plays a central role in many common metabolic disorders. Yet despite decades of research, understanding of human liver metabolism remains incomplete. The majority of studies to date have been based on animal or cell culture models that do not fully recapitulate human physiology.
This paper published in Nature Metabolism – authored by Sapient’s scientists and our key collaborators and to which Sapient contributed mass spectrometry data – details the comprehensive analysis of human liver tissue ex vivo, allowing for the measure of human liver metabolism with great depth and resolution in an experimentally tractable system.
By employing global 13C tracing, nontargeted mass spectrometry, and model-based metabolic flux analysis, the researchers were able to measure a wide range of metabolic pathways within intact human liver tissue.
This approach not only confirmed well-known aspects of liver metabolism but also uncovered unexpected activities such as de novo creatine synthesis and branched-chain amino acid transamination, highlighting significant differences from rodent models.
The study represents a significant advancement in furthering our understanding of human liver metabolism, offering critical insights into the pathology of metabolic diseases. This has promising implications for target discovery, toxicity assessment, and targeted therapeutic development.