Regional Metabolomics and Fluxomics Core at Princeton

Overview

The DRC Regional Metabolomics and Fluxomics Core at Princeton was founded in 2012 to meet the needs of Penn DRC investigators to measure, both broadly and quantitatively, metabolic activity in systems of importance for understanding diabetes and obesity. The Core employs mass spectrometry infrastructure and analytical chemistry expertise at Princeton University to provide Penn DRC investigators access to state-of-the-art metabolomics and flux analysis. The Core’s methods cover a wide array of diabetes-relevant metabolites and pathways, including glycolysis, gluconeogenesis, glycogen turnover, fat synthesis, and amino acid metabolism. Methods cover, with proper choice of isotope tracers, metabolite levels, pathway activities, and/or pathway substrate inputs. To emphasize the Core’s distinctive capability in measuring metabolic flux through in vivo isotope tracer infusions, “Fluxomics” was recently added to its name. To augment the Core’s capacity, we are developing MALDI imaging mass spectrometry methods for spatially resolved metabolomics and fluxomics.

Objective

The primary objective of the Regional Metabolomics and Fluxomics Core is to provide DRC members with state-of-the-art metabolomics and flux analysis services, including pioneering capabilities like spatial fluxomics.

Core Aims

• Metabolome and Lipidome Quantitation: The Core is a recognized leader in metabolomics and lipidomics. The primary analytical methodology is liquid chromatography-mass spectrometry (LC-MS).
• Isotope Tracer Studies: Metabolite abundances are informative, but do not reveal pathway activities: Metabolite levels can increase due to faster production or slower consumption. The Core brings world-leading expertise in tracer study design, labeling pattern measurement, and data interpretation for both cell culture and in vivo research. Over the past several years, these capabilities have been extensively utilized by DRC investigators to probe in vivo metabolic fluxes in mouse models of obesity and diabetes, resulting in numerous high impact publications.
• Spatial Metabolomics and Fluxomics: We see the next frontier as making metabolomic and fluxomic measurements in a spatially resolved manner, e.g. to distinguish glycolytic, gluconeogenic, and lipogenic cells within the liver.

In all, the Regional Metabolomics Core provides DRC investigators with access to state-of-the-art approaches to metabolite and metabolic flux analysis, including new capabilities in spatially-resolved analyses. These capabilities support groundbreaking DRC science involving preclinical and clinical studies relating to the etiology and treatment of diabetes, obesity, and related metabolic disorders.

Services

The Rabinowitz lab maintains three LC-Orbitrap systems, each with capacity for 50 samples per day (on top of blanks and quality control samples), resulting in total capacity of 1000 samples per week. DRC usage has been steady at about 100 samples per week. These samples are accommodated by dedicated time of up to 1 day/week on each of these three LC-MS systems. For sets of up to 40 samples, instrument time has reliably been scheduled within 2 weeks of User request, returning data within 3 weeks. Experiments involving larger number of samples are coordinated with other User instrument needs. Often such samples can also be run within 2 weeks, but sometimes they must be delayed a few weeks to find a gap in the schedule. In the case of very large sample requests (> 300 samples), these are vetted by Rabinowitz for centrality to the DRC mission and any concerns discussed with DRC Director Lazar.