Case Mouse Metabolic Phenotyping Center

摘要

ABSTRACT The mission of the Case-MMPC is to facilitate phenotypic characterization of mice for investigators studying metabolic diseases, with an emphasis and prioritization on diabetes and obesity. We work within the MMPC Consortium to complement and partially overlap the activities of the other six Centers. Our niche is the measurement and interpretation of metabolic fluxes and metabolomic patterns with the help of stable isotope tracer techniques and mass spectrometry, with emphasis on the avoidance of artifacts that often plague such protocols. The combination of metabolomics and stable isotope technology allows the discovery of new pathways and new regulatory mechanisms. This approach was pioneered at the Case-MMPC and has since gained favor with investigators around the world. Our Center was also instrumental in the development of the NIDDK-sponsored annual course on “Use of Isotopes for Metabolic Studies”, which will be taught for the 8th time in November 2015 by 11 faculty from MMPCs and US universities, and draws an international attendance. The Case-MMPC is currently in its 9th year of operation. This application requests support for increasing the capacity of the Center, expanding the repertoire of tracers provided and metabolites measured to include oxidative stress and inflammation-related pathways. Specific Aim 1 will provide core facilities for investigators to carry out metabolic flux experiments, utilizing our expertise in stable isotope tracers and mass spectrometry. Aim 2 will conduct analyses of murine tissues and body fluids provided by investigators carrying out metabolic studies. This includes investigators working at CWRU and in other institutions, domestic and globally. In Aim 3 we will develop additional innovative tracer and methodological approaches for assessing oxidative stress and inflammation. This involves a new “sub-core” that will also provide custom synthesis of stable isotopic tracers and mass spectrometric analysis of lipid peroxidation products. In Aim 4 we will provide training and education to investigators and their staff for, (i) proficiency in the use of isotopes for metabolic studies, (ii) understanding the capabilities of the MMPC and designing appropriate experiments for their questions, (iii) carrying out procedures in their laboratory for preparing samples to be analyzed by the MMPC, and/or (iv) learning to carrying out the complete procedure in their own laboratories. The implementation of these aims is expected to significantly advance the field of metabolism and assist investigators in Cleveland, nationally and globally, to discover new pathways and mechanisms that cause diabetes and obesity- related chronic diseases.