Summary of Study ST003175
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 PR001974. The data can be accessed directly via it's Project DOI: 10.21228/M8K13N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST003175 |
| Study Title | Inactivation of mitochondrial MUL1 E3 ubiquitin ligase inhibits lipogenesis and prevents diet-induced obesity in mice |
| Study Type | Basic Research |
| Study Summary | Characterize the role of mitochondrial MUL1 E3-ubiquitin ligase on energy metabolism and lipogenesis using Mul1 deficient, Mul1(-/-), mice. MUL1 protein is involved in mitochondrial dynamics, and innate immune response but its primary function might be the regulation of lipogenesis under conditions of nutritional overload. Using metabolic cages, we monitored whole body energy expenditure, metabolism, and thermoregulation of the Mul1(-/-) mice under standard diet (ND) or high fat diet (HFD). We examined the effect of Mul1 inactivation on body weight, HFD-induced adiposity, fatty liver, glucose intolerance, and insulin resistance. We performed global metabolomics, lipidomic, and genome-wide mRNA sequencing using liver from Mul1(+/+) and Mul1(-/-) animals on HFD. The expression level of key proteins involved in lipogenesis and their regulation in the absence of MUL1 was monitored by SDS-PAGE and Western blot analysis. We found that Mul1(-/-) animals have a metabolic phenotype that confers robust resistance to HFD-induced obesity. Several metabolic and lipidomic pathways are perturbed in the liver of Mul1(-/-) animals on HFD, particularly the one driven by Stearoyl-CoA Desaturase 1 (SCD1), a key regulator of lipid metabolism and obesity. In addition, key enzymes involved in lipogenesis and fatty acid oxidation such as ACC1, FASN, AMPK, and CTP1 were also modulated. The concerted deregulation of these enzymes, in the absence of MUL1, causes reduced fat storage and increased fatty acid oxidation. We identified a new function of mitochondrial MUL1 E3 ubiquitin ligase in the regulation of lipogenesis and adiposity, particularly during conditions of HFD. Inactivation of MUL1 provides resistance to HFD-induced obesity and can be a therapeutic target for the treatment of obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD). |
| Institute | University of Florida |
| Last Name | Merritt |
| First Name | Matthew |
| Address | SW ARCHER RD, Gainesville, FL 32611 |
| rmahar@hnbgu.ac.in | |
| Phone | 9557559849 |
| Submit Date | 2024-04-10 |
| Num Groups | 2 |
| Total Subjects | 12 |
| Num Males | 6 |
| Num Females | 6 |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-04-19 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN005211 | AN005212 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 |
| Column | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | A.U. | A.U. |
Chromatography:
| Chromatography ID: | CH003942 |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Waters ACQUITY UPLC BEH C18 (100 x 2.1mm,1.7um) |
| Column Temperature: | 50 |
| Flow Gradient: | 0−0.5 min, 60% B; 0.5−2 min, 60−95% B; 2−17 min, 95% B; 17−17.5 min, 95−60% B; 17.5−20 min, 60% B |
| Flow Rate: | 350 µl/min |
| Solvent A: | 60:40 acetonitrile:water; 10mM ammonium formate; 0.1% formic acid |
| Solvent B: | 90:8:2 2-propanol:acetonitrile:water; 10mM ammonium formate; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
