Summary of Study ST002361
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001516. The data can be accessed directly via it's Project DOI: 10.21228/M8R12T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002361 |
| Study Title | UCP2-dependent redox-sensing in POMC neurons regulates feeding |
| Study Summary | Paradoxically, glucose, the primary driver of satiety, activates a small population of anorexigenic POMC neurons. Here we show that lactate levels in the circulation and in the cerebrospinal fluid are elevated in fed state and addition of lactate to glucose activates the majority of POMC neurons while increasing cytosolic NADH generation, mitochondrial respiration and extracellular pyruvate levels. Inhibition of lactate dehydrogenases diminishes mitochondrial respiration, NADH production, and POMC neuronal activity. However, inhibition of the mitochondrial pyruvate carrier has no effect. POMC-specific downregulation of Ucp2 (Ucp2PomcKO), a molecule regulated by fatty acid metabolism and shown to play a role as transporter in the malate-aspartate shuttle, abolishes lactate- and glucose-sensing of POMC neurons. Ucp2PomcKO mice have impaired glucose metabolism and are prone to obesity on a high fat diet. Altogether, our data show that lactate through redox signaling and blocking mitochondrial glucose utilization activates POMC neurons to regulate feeding and glucose metabolism. |
| Institute | Columbia University |
| Last Name | Diano |
| First Name | Sabrina |
| Address | 1150 St. Nicholas Avenue Russ Berrie Medical Science Pavilion Rm 405 New York, NY, 10032 |
| sd3449@cumc.columbia.edu | |
| Phone | 212 8514554 |
| Submit Date | 2022-11-28 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-12-15 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003855 | AN003856 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Unspecified |
| Chromatography system | SCIEX ExionLC | SCIEX ExionLC |
| Column | Phenomenex Kinetex F5 Core-shell LC (100 x 2.1 mm,2.6um) | Thermo Scientific Hypercarb (100 x 4.6 mm,3um) |
| MS Type | ESI | ESI |
| MS instrument type | Triple TOF | Triple TOF |
| MS instrument name | ABI Sciex 6600 TripleTOF | ABI Sciex 6600 TripleTOF |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | peak area | peak area |
MS:
| MS ID: | MS003596 |
| Analysis ID: | AN003855 |
| Instrument Name: | ABI Sciex 6600 TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | Data were collected using an information-dependent analysis (IDA) workflow consisting of a TOF MS scan (200 msec) and a high-resolution IDA experiment (70 msec each) monitoring 10 candidate ions per cycle. Former target ions were excluded after 2 occurrences for 5 seconds and dynamic background subtraction was employed. The mass range for both TOF MS and IDA MS/MS scans was 60-1000. Ion spray voltage = 5000 V; ion source gas 1 (GS1) = 50 psi, ion source gas 2 (GS2) = 50 psi, curtain gas (CUR) = 30 psi, temperature (TEM) = 400 oC. declustering potential (DP) = 35 V, collision energy (CE) = 30 V, collision energy spread (CES) = 20 V. El-MAVEN software (Elucidata.io) was used for peak picking and curation from house built targeted and untargeted libraries. Targeted libraries were developed using a commercial standard kit of ~600 metabolites (IROA Technologies) in each mode, yielding reference data (molecular ions and retention times) with wide coverage of the endogenous metabolome. Untargeted libraries contained ~2,700 metabolites drawn from the KEGG database where the top 5 candidates with the highest intensity throughout a sample run for each metabolite were automatically curated. |
| Ion Mode: | POSITIVE |
| MS ID: | MS003597 |
| Analysis ID: | AN003856 |
| Instrument Name: | ABI Sciex 6600 TripleTOF |
| Instrument Type: | Triple TOF |
| MS Type: | ESI |
| MS Comments: | Data were collected using an information-dependent analysis (IDA) workflow consisting of a TOF MS scan (200 msec) and a high-resolution IDA experiment (70 msec each) monitoring 10 candidate ions per cycle. Former target ions were excluded after 2 occurrences for 5 seconds and dynamic background subtraction was employed. The mass range for both TOF MS and IDA MS/MS scans was 70-1000. Ion spray voltage = -4500V, ion source gas 1 (GS1) = 50 psi, ion source gas 2 (GS2) = 50 psi, curtain gas (CUR) = 30 psi, temperature (TEM) = 500 oC.declustering potential (DP) = 35 V, collision energy (CE) = 30 V, collision energy spread (CES) = 20 V. El-MAVEN software (Elucidata.io) was used for peak picking and curation from house built targeted and untargeted libraries. Targeted libraries were developed using a commercial standard kit of ~600 metabolites (IROA Technologies) in each mode, yielding reference data (molecular ions and retention times) with wide coverage of the endogenous metabolome. Untargeted libraries contained ~2,700 metabolites drawn from the KEGG database where the top 5 candidates with the highest intensity throughout a sample run for each metabolite were automatically curated. |
| Ion Mode: | NEGATIVE |
