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
Email	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

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Sample Preparation:

Sampleprep ID:	SP002456
Sampleprep Summary:	Cells cultured in 6-well plates were quickly washed once with ice cold 5 mM HEPES, then immediately quenched in 150ul/well ice cold quench buffer (20% methanol, 3 mM sodium fluoride, 0.1% formic acid, 1mM phenylalanine and 100uM EDTA). Each well was harvested using a cell lifter and immediately transferred to a pre-chilled 96-well plate on dry ice. Once completely frozen, cell lysates were lyophilized and stored in the -80oC freezer until the sample run. Lyophilized samples were prepared by resuspending in 50 µL water with D4-taurine (50 µM) as an internal standard and 5 µL of the supernatant was injected for each analysis mode using high performance liquid chromatography (HPLC) into the 6600 Triple TOF LC-MS/MS mass spectrometer (Sciex).

Sampleprep ID:

SP002456

Sampleprep Summary:

Cells cultured in 6-well plates were quickly washed once with ice cold 5 mM HEPES, then immediately quenched in 150ul/well ice cold quench buffer (20% methanol, 3 mM sodium fluoride, 0.1% formic acid, 1mM phenylalanine and 100uM EDTA). Each well was harvested using a cell lifter and immediately transferred to a pre-chilled 96-well plate on dry ice. Once completely frozen, cell lysates were lyophilized and stored in the -80oC freezer until the sample run. Lyophilized samples were prepared by resuspending in 50 µL water with D4-taurine (50 µM) as an internal standard and 5 µL of the supernatant was injected for each analysis mode using high performance liquid chromatography (HPLC) into the 6600 Triple TOF LC-MS/MS mass spectrometer (Sciex).