Summary of project PR001516

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

Project ID: PR001516
Project DOI:doi: 10.21228/M8R12T
Project Title:UCP2-dependent redox-sensing in POMC neurons regulates feeding
Project 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

Summary of all studies in project PR001516

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ST002361 UCP2-dependent redox-sensing in POMC neurons regulates feeding Mus musculus Columbia University MS 2022-12-15 1 8 Uploaded data (7.1G)*
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