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 |
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Collection:
| Collection ID: | CO002443 |
| Collection Summary: | Hypothalamic primary neuronal cell culture Eight to ten neonatal (0 days old) pubs from either control or Ucp2PomcKO mice derived from homozygous Cre-positive parents were used for hypothalamic primary neuronal cell culture. In brief, we carefully removed the brain's hypothalamus and placed it onto a small culture dish containing a small volume of Hibernate-A Medium (Cat# A1247501, Thermo Fisher Scientific). After digestion, the tissues dissociated to single cells with 6 mL of Hibernate-A Medium containing 2.5 % of Trypsin-EDTA for 15 minutes at 37℃. Suspended cells were filtered (40 μm) and centrifuged for 5 min at 1000 rpm. The pellet was re-suspended and plated on XF96 cell culture microplates (Cat# 101085-004, Agilent Technologies) coated with poly-D-lysine (Cat# P6407, Sigma-Aldrich) at a density of 0.2 x104 cells per well. Cells were cultured in Neurobasal-A medium (Cat# 10888022, Thermo Fisher Scientific) supplemented with 1 % penicillin-streptomycin, 2 % B-27 Supplement (Cat# 17504044, Thermo Fisher Scientific), and GlutaMAX-I (Cat# 35050061, Thermo Fisher Scientific), CultureOne supplement (Cat# A3320201, Thermo Fisher Scientific). For control culture, we used either Ucp2fl/fl; Pomc-CreERT2; tdTomato mice which neuronal cultures were treated with vehicle (0.03 % ethanol diluted in medium) or Ucp2+/+; Pomc-CreERT2; tdTomato mice which neuronal cultures were treated with 2 μM 4-hydroxytamoxifen (Cat# H7904, Sigma-Aldrich). After 10 days in culture, primary neuronal cells isolated from control and Ucp2PomcKO mice were treated with 2 μM 4-hydroxytamoxifen for expression of a CreER recombinase. Primary neuronal cells were used for the measurement of mitochondria oxidation two days later. |
| Sample Type: | Neurons |
