Summary of project PR002599
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 PR002599. The data can be accessed directly via it's Project DOI: 10.21228/M8PZ5N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002599 |
| Project DOI: | doi: 10.21228/M8PZ5N |
| Project Title: | Portal Vein Enriched Metabolites as Intermediate Regulators of the Gut Microbiome in Insulin Resistance |
| Project Summary: | Diet and obesity significantly contribute to insulin resistance and type 2 diabetes, in part via the gut microbiome. To explore the role of gut-derived metabolites on host metabolism, we assessed portal/peripheral blood metabolites in mice with different risks of obesity/diabetes challenged with high-fat diet (HFD) +/- antibiotics. In diabetes/obesity-prone C57Bl/6J mice, 111 were portally-enriched and 74 were peripherally-enriched, many of which differed in metabolic-syndrome-resistant 129S1/129S6 mice. Vancomycin treatment of HFD-fed C57Bl/6J mice modified the microbiome and portal/peripheral ratio of many metabolites, including upregulating multiple TCA cycle-related metabolites, like mesaconate, in portal blood. Treatment of hepatocytes in vitro with mesaconate and its isomers (itaconate, citraconate) improved insulin signaling and transcriptionally regulated genes involved in gluconeogenesis, fatty acid oxidation and lipogenesis both in vitro and in vivo. Thus, portal vs. peripheral metabolites play important roles in mediating effects of the microbiome on hepatic metabolism and the pathogenesis of HFD-related insulin resistance. This data deposition contains two studies: one assessing the role of diet and the microbiome on portal metabolites, and another estimating the role of genetic background on portal-enriched metabolites. |
| Institute: | Broad Institute of MIT and Harvard |
| Department: | Metabolomics Platform |
| Last Name: | Kahn |
| First Name: | Ronald |
| Address: | One Joslin Place, Boston, MA 02215 |
| Email: | c.ronald.kahn@joslin.harvard.edu |
| Phone: | (617) 309-2635 |
| Funding Source: | R01DK121967, R01DK031036, R01DK128429, P30DK036836 (to Joslin Diabetes Center), the Mary K. Iacocca Professorship (to C.R.K), and the FAPESP Process No.: 2022/05957-0 |
| Project Comments: | Two part study (Part 1) |
| Contributors: | Vitor Rosetto Muñoz, Francois Moreau, Marion Soto, Loc Duyen Pham, Jimmy Zhong, Sam Zimmerman, Bruna B. Brandao, Khyati Girdhar, Julian Avila, Hui Pan, Jonathan Dreyfuss, Emrah Altindis, Aleksandar Kostic, Clary B. Clish, C. Ronald Kahn |
Summary of all studies in project PR002599
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004132 | Metabolite profiling of portal plasma, cardiac puncture plasma, and cecal contents of 129 T, 129 J, C57Bl6 mice. | Mus musculus | Broad Institute of MIT and Harvard | MS* | 2025-09-02 | 1 | 54 | Uploaded data (35.5G)* |
| ST004133 | Metabolite profiling of portal and cardiac puncture plasma in C57Bl6 mice treated with Vancomycin or Metronidazole under a regular or high fat diet. | Mus musculus | Broad Institute of MIT and Harvard | MS* | 2025-09-02 | 1 | 62 | Uploaded data (28.2G)* |
