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 #
5U24DK076174-02
Application #
8379010
Study Section
Special Emphasis Panel (ZDK1-GRB-S)
Project Start
2012-07-01
Project End
2016-05-31
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
2
Fiscal Year
2012
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
Ko, Chih-Wei; Counihan, Daniel; Wu, Jing et al. (2018) Macrophages with a deletion of the phosphoenolpyruvate carboxykinase 1 (Pck1) gene have a more proinflammatory phenotype. J Biol Chem 293:3399-3409
Bederman, Ilya R; Pora, Gavriella; O'Reilly, Maureen et al. (2018) Absence of leptin signaling allows fat accretion in cystic fibrosis mice. Am J Physiol Gastrointest Liver Physiol 315:G685-G698
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
Mosinski, J D; Pagadala, M R; Mulya, A et al. (2016) Gastric bypass surgery is protective from high-fat diet-induced non-alcoholic fatty liver disease and hepatic endoplasmic reticulum stress. Acta Physiol (Oxf) 217:141-51
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
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
Mera, Paula; Laue, Kathrin; Ferron, Mathieu et al. (2016) Osteocalcin Signaling in Myofibers Is Necessary and Sufficient for Optimum Adaptation to Exercise. Cell Metab 23:1078-1092
Majumder, Mithu; Mitchell, Daniel; Merkulov, Sergei et al. (2015) Residues required for phosphorylation of translation initiation factor eIF2? under diverse stress conditions are divergent between yeast and human. Int J Biochem Cell Biol 59:135-41
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
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

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