Core C: Analytical &Metabolomic The Case MMPC specializes in the use of stable isotopes, mass spectrometry and metabolomics to investigate the regulation of pathways of intermediary metabolism in vivo and ex vivo. Emphasis is on quantitative measurements of inter-organ and intra-organ carbon fluxes. Our strategy links clinical-type studies (limited to body fluids) and pure biochemical studies (such as the kinetics of purified enzymes). The association of metabolomics and mass isotopomer analysis provides a wealth of information on the regulation of known pathways. It also allows to identify new pathways. Metabolomics developed initially as a non-targeted strategy aimed at gathering sufficient data on a (patho)physiological process (biomarkers), so that one could formulate hypotheses to be tested. A variant of this strategy is to target metabolomic studies to classes of compounds, the concentrations and labeling patterns of which can provide much new information: citric acid cycle intermediates, (hydroxy)acids, acyl-CoA esters, acylcarnitine esters. The Case MMPC occupies a specialized niche in the MMPC consortium, complementing the expertise of the other centers, but with a healthy degree of overlap with the Vanderbiit, Yale, Dallas and Cincinnati centers.
The specific aims of the Analytical &Metabolomic Core are: 1. To help users in the design, implementation, analytical procedures and interpretation of metabolic studies conducted either, (i) entirely in the user's lab, (ii) entirely in the Case MMPC, or (iii) partly in the user's lab (animal experiments) and partly in the MMPC (analyses of tissues and body fluids shipped from the user's lab). 2. To set up, at users'request, tests and analytical procedures not currently listed on the web page of the Case MMPC. 3. To develop analytical techniques and isotopic strategies in anticipation of users'needs. 4. To train US and foreign scientists in the proper use of isotopes for metabolic studies. This training takes to form of (i) mentoring individual users, and (ii) contribution to an annual MMPC course.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Resource-Related Research Projects--Cooperative Agreements (U24)
Project #
5U24DK076174-04
Application #
8708044
Study Section
Special Emphasis Panel (ZDK1-GRB-S)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
4
Fiscal Year
2014
Total Cost
$407,517
Indirect Cost
$147,952
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Mera, Paula; Laue, Kathrin; Ferron, Mathieu et al. (2016) Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell Metab 23:1078-92
Roychowdhury, Sanjoy; McCullough, Rebecca L; Sanz-Garcia, Carlos et al. (2016) Receptor interacting protein 3 protects mice from high-fat diet-induced liver injury. Hepatology 64:1518-1533
Li, Lei; Che, Li; Wang, Chunmei et al. (2016) [(11)C]acetate PET Imaging is not Always Associated with Increased Lipogenesis in Hepatocellular Carcinoma in Mice. Mol Imaging Biol 18:360-7
Palczewski, Grzegorz; Widjaja-Adhi, M Airanthi K; Amengual, Jaume et al. (2016) Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism. J Lipid Res 57:1684-95
Majumder, Mithu; Mitchell, Daniel; Merkulov, Sergei et al. (2015) Residues required for phosphorylation of translation initiation factor eIF2α under diverse stress conditions are divergent between yeast and human. Int J Biochem Cell Biol 59:135-41
Cordoba-Chacon, Jose; Majumdar, Neena; List, Edward O et al. (2015) Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice. Diabetes 64:3093-103
Zhang, Yifan; Zhang, Shenghui; Marin-Valencia, Isaac et al. (2015) Decreased carbon shunting from glucose toward oxidative metabolism in diet-induced ketotic rat brain. J Neurochem 132:301-12
Li, Qingling; Deng, Shuang; Ibarra, Rafael A et al. (2015) Multiple mass isotopomer tracing of acetyl-CoA metabolism in Langendorff-perfused rat hearts: channeling of acetyl-CoA from pyruvate dehydrogenase to carnitine acetyltransferase. J Biol Chem 290:8121-32
DeSantis, David A; Ko, Chih-Wei; Wang, Lan et al. (2015) Constitutive Activation of the Nlrc4 Inflammasome Prevents Hepatic Fibrosis and Promotes Hepatic Regeneration after Partial Hepatectomy. Mediators Inflamm 2015:909827
Frederick, David W; Davis, James G; Dávila Jr, Antonio et al. (2015) Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism. J Biol Chem 290:1546-58

Showing the most recent 10 out of 37 publications