Summary of Study ST002204
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 PR001407. The data can be accessed directly via it's Project DOI: 10.21228/M8V995 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 | ST002204 |
| Study Title | Endothelial Sirtuin1 Suppresses Whole-body Insulin Sensitivity by Modulating the Secretome |
| Study Type | End point |
| Study Summary | Sirtuin1 (Sirt1) in skeletal muscle (SK) and fat protects against metabolic damage by stimulating insulin sensitivity. Here we report that mice with selective deletion of endothelial Sirt1 (E-Sirt1-KO) paradoxically exhibit heightened whole-body insulin sensitivity. Akt phosphorylation, glucose uptake, and glycolysis are boosted in SK and brown adipose tissue (BAT) of E-Sirt1-KO mice. E-Sirt1-KO mice have higher energy expenditure and are partially protected from high-fat diet-induced insulin resistance. Enhanced insulin sensitivity and peripheral tissue Akt phosphorylation in E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation after surgical parabiosis. Silencing of Sirt1 in endothelial cells upregulates transcription of the F-actin-binding protein thymosin beta-4 (Tβ4), whose secretion activates Akt in skeletal myotubes. Sirt1 downregulation stimulates endothelial Tβ4 transcription through inhibition of autophagy and upregulation of nuclear factor-kappa B signaling. Thus, unlike Sirt1 in skeletal muscle and fat, endothelial Sirt1 curtails whole-body insulin sensitivity by inhibiting expression of secreted Tβ4 |
| Institute | University of Iowa |
| Department | Internal medicine |
| Laboratory | irani |
| Last Name | Irani |
| First Name | Kaikobad |
| Address | RM 2256 CBRB, Newton Rd, Iowa City, IA 52242 |
| kaikobad-irani@uiowa.edu | |
| Phone | 3193358821 |
| Submit Date | 2021-12-02 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | cdf |
| Analysis Type Detail | GC-MS |
| Release Date | 2022-07-22 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Sample Preparation:
| Sampleprep ID: | SP002296 |
| Sampleprep Summary: | Tissue samples were lyophilized overnight prior to bead mill homogenization in 18:1 (µl:mg wet tissue weight) ice-cold 2:2:1 methanol:acetonitrile:water extraction buffer containing a mixture of internal standards (D4-citric acid, D4-succinic acid, D8-valine, and U13C-labeled glutamine, glutamic acid, lysine, methionine, serine, and tryptophan; Cambridge Isotope Laboratories). Homogenates were rotated for 1 hour at -20°C. Homogenates were centrifuged for 10 minutes at 21,000 x g, and 150 µl of the cleared metabolite extracts were transferred to autosampler vials and dried using a SpeedVac vacuum concentrator (Thermo). Dried metabolite extracts were reconstituted in 30 μl of 11.4 mg/ml methoxyamine (MOX) in anhydrous pyridine, vortexed for 5 minutes, and heated for 1 hour at 60°C. Next, to each sample 20 μl of N,O-Bis(trimethylsilyl)trifluoroacetamide (TMS) was added, samples were vortexed for 1 minute, and heated for 30 minutes at 60°C. |
| Sampleprep Protocol Filename: | GC_Method_Tissue.pdf |
