Clinical lipidomics - A community-driven roadmap to translate research into clinical applications.

Lipid metabolites, beyond triglycerides and cholesterol, have been shown to have vast potential for applications in clinical applications, with substantial societal and economical value. To successfully evolve from the current research-grade methods to assays suitable for routine clinical applications, a harmonization - if not standardization - of these mass spectrometry-based workflows is necessary. Input on clinical needs and technological capabilities must be obtained from all relevant stakeholders, including wet lab scientists, informaticians and data scientists, manufacturers, and medical professionals.

Loss of hepatic Mboat7 leads to liver fibrosis.

Objective: The rs641738C>T variant located near the membrane-bound O-acyltransferase domain containing 7 (MBOAT7) locus is associated with fibrosis in liver diseases, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease, hepatitis B and C. We aim to understand the mechanism by which the rs641738C>T variant contributes to pathogenesis of NAFLD.

Design: Mice with hepatocyte-specific deletion of MBOAT7 (Mboat7) were generated and livers were characterised by histology, flow cytometry, qPCR, RNA sequencing and lipidomics.

Kinetic modelling of quantitative proteome data predicts metabolic reprogramming of liver cancer.

Background: Metabolic alterations can serve as targets for diagnosis and cancer therapy. Due to the highly complex regulation of cellular metabolism, definite identification of metabolic pathway alterations remains challenging and requires sophisticated experimentation.

Methods: We applied a comprehensive kinetic model of the central carbon metabolism (CCM) to characterise metabolic reprogramming in murine liver cancer.

Shotgun Lipidomics Combined with Laser Capture Microdissection: A Tool To Analyze Histological Zones in Cryosections of Tissues.

Shotgun analysis provides a quantitative snapshot of the lipidome composition of cells, tissues, or model organisms; however, it does not elucidate the spatial distribution of lipids. Here we demonstrate that shotgun analysis could quantify low-picomole amounts of lipids isolated by laser capture microdissection (LCM) of hundred micrometer-sized histological zones visualized at the cryosections of tissues. We identified metabolically distinct periportal (pp) and pericentral (pc) zones by immunostaining of 20 μm thick cryosections of a healthy mouse liver.

Salt-responsive gut commensal modulates T17 axis and disease.

A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (T17) cells, which can also contribute to hypertension. Induction of T17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown.