Summary of Study ST003376
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 PR002094. The data can be accessed directly via it's Project DOI: 10.21228/M8Z221 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 | ST003376 |
| Study Title | Bempedoic acid improves diet-induced steatosis independent of hepatic ACLY |
| Study Summary | To test the effect of BPA on hepatic steatosis, we placed WT and LAKO mice on WD for 6 weeks, with 10 mg/kg BPA daily oral gavage over the last 3 weeks, a dose previously shown to be effective in reducing steatosis. Quantification of lipids by mass spectrometry demonstrated that ACLY deficiency increased abundance of TAGs and DAGs, while BPA treatment reduced these lipids in both genotypes. Moreover, ACLY deficiency reduced phospholipid (PC and PE) abundance. |
| Institute | Salk Institute for Biological Studies |
| Last Name | KUNA |
| First Name | RAMYA |
| Address | 10010 N Torrey Pines Rd, La Jolla, California, 92037, USA |
| rkuna@salk.edu | |
| Phone | 8584534100 |
| Submit Date | 2024-08-05 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-08-06 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002094 |
| Project DOI: | doi: 10.21228/M8Z221 |
| Project Title: | Bempedoic acid suppresses diet-induced hepatic steatosis independent of ACLY |
| Project Summary: | ATP citrate lyase (ACLY) synthesizes acetyl-CoA for de novo lipogenesis (DNL), which is elevated in metabolic dysfunction-associated steatotic liver disease. Hepatic ACLY is inhibited by the LDL-cholesterol lowering drug bempedoic acid (BPA), which also improves steatosis in mice. Indeed, BPA potently suppresses hepatic DNL and increases fat catabolism. However, it is unclear if ACLY is the relevant molecular target in reducing liver triglyceride, particularly since the acetyl-CoA synthetase ACSS2 can compensate for ACLY deficiency to provision acetyl-CoA for DNL. We show that on a Western diet, loss of hepatic ACLY alone or ACLY and ACSS2 together unexpectedly exacerbates steatosis, linked to reduced hepatic abundance of endogenous PPAR ligands and lower expression of PPAR target genes controlling fatty acid oxidation. Importantly, BPA treatment ameliorates WD-mediated triglyceride accumulation in both WT and liver ACLY knockout mice, indicating that its primary effects on hepatic lipid metabolism are independent of ACLY. Together, these data indicate that hepatic ACLY plays an unexpected role in restraining diet-dependent lipid accumulation, and that BPA improves steatosis independent of ACLY. |
| Institute: | Salk Institute for Biological Studies |
| Department: | Molecular and Cell Biology Laboratory |
| Laboratory: | Metallo Lab |
| Last Name: | Kuna |
| First Name: | Ramya |
| Address: | 10010 N Torrey Pines Rd, La Jolla, California, 92037, USA |
| Email: | rkuna@salk.edu |
| Phone: | 8582038321 |
Subject:
| Subject ID: | SU003497 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Sample source | Group |
|---|---|---|---|---|
| SA367123 | Alb_1994_21_KO BPA | LACLYKO | Liver | BPA |
| SA367124 | Alb_1990_17_KO BPA | LACLYKO | Liver | BPA |
| SA367125 | Alb_1989_16_KO BPA | LACLYKO | Liver | BPA |
| SA367126 | Alb_1986_13_KO BPA | LACLYKO | Liver | BPA |
| SA367127 | Alb_1984_11_KO BPA | LACLYKO | Liver | BPA |
| SA367128 | Alb_1981_8_KO BPA | LACLYKO | Liver | BPA |
| SA367129 | Alb_1977_4_KO BPA | LACLYKO | Liver | BPA |
| SA367130 | Alb_1985_12_KO Vehicle | LACLYKO | Liver | Vehicle |
| SA367131 | Alb_1993_20_KO Vehicle | LACLYKO | Liver | Vehicle |
| SA367132 | Alb_1992_19_KO Vehicle | LACLYKO | Liver | Vehicle |
| SA367133 | Alb_1987_14_KO Vehicle | LACLYKO | Liver | Vehicle |
| SA367134 | Alb_1980_7_KO Vehicle | LACLYKO | Liver | Vehicle |
| SA367135 | Alb_1979_6_KO Vehicle | LACLYKO | Liver | Vehicle |
| SA367136 | Alb_1975_2_KO Vehicle | LACLYKO | Liver | Vehicle |
| SA367137 | Alb_1997_24_WT BPA | Wild-type | Liver | BPA |
| SA367138 | Alb_1995_22_WT BPA | Wild-type | Liver | BPA |
| SA367139 | Alb_1991_18_WT BPA | Wild-type | Liver | BPA |
| SA367140 | Alb_1988_15_WT BPA | Wild-type | Liver | BPA |
| SA367141 | Alb_1982_9_WT BPA | Wild-type | Liver | BPA |
| SA367142 | Alb_1976_3_WT BPA | Wild-type | Liver | BPA |
| SA367143 | Alb_1978_5_WT Vehicle | Wild-type | Liver | Vehicle |
| SA367144 | Alb_3703_25_WT Vehicle | Wild-type | Liver | Vehicle |
| SA367145 | Alb_1996_23_WT Vehicle | Wild-type | Liver | Vehicle |
| SA367146 | Alb_1983_10_WT Vehicle | Wild-type | Liver | Vehicle |
| SA367147 | Alb_1974_1_WT Vehicle | Wild-type | Liver | Vehicle |
| Showing results 1 to 25 of 25 |
Collection:
| Collection ID: | CO003490 |
| Collection Summary: | Liver samples were collected using Wollenberger clamps pre-cooled to the temperature of liquid nitrogen and stored at -80 C until analysis. |
| Sample Type: | Liver |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR003506 |
| Treatment Summary: | BPA(Bempedoic acid) was first prepared as a disodium salt aqueous solution by making a 2:1 molar ratio of NaOH to BPA in water. While stirring, carboxymethylcellulose (Sigma-Aldrich C5678) was added at a final concentration of 0.5% w/v. Tween-20 was added at a final concentration of 0.025%. pH was measured and adjusted with HCl to pH 7. Vehicle solution was prepared with the same method, excluding BPA. BPA or vehicle was administered to mice daily in the morning by oral gavage at either 10 or 30 mg/kg body weight or equivalent vehicle volume for indicated lengths of time. The last dose of BPA was administered 2-4 hours prior to tissue collection. |
| Treatment Compound: | BPA |
Sample Preparation:
| Sampleprep ID: | SP003504 |
| Sampleprep Summary: | Samples were extracted with 400 ul of methanol (-20 C), 100 ul of water (ice-cold), 400 saline (ice-cold), and 1000 ul of chloroform (-20 C). |
| Processing Storage Conditions: | Room temperature |
| Extract Storage: | 4℃ |
Combined analysis:
| Analysis ID | AN005528 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Thermo Vanquish |
| Column | Thermo Accucore C30 (150 x 2.1mm,2.6um) |
| MS Type | ESI |
| MS instrument type | Ion trap |
| MS instrument name | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE |
| Units | relative abundance per mg tissue |
Chromatography:
| Chromatography ID: | CH004204 |
| Chromatography Summary: | 30% to 43% B from 3-8 min, then from 43% to 50% B from 8-9 min, then 50-90% B from 9-18 min, then 90-99% B from 18-26 min, then held at 99% B from 26-30 min, before returning to 30% B in 6 min and held for a further 4 min |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Thermo Accucore C30 (150 x 2.1mm,2.6um) |
| Column Temperature: | 40 |
| Flow Gradient: | 0 min, 30% B; 3 min, 30% B; 8 min, 43% B; 9 min, 50% B; 18 min, 90% B; 26 min, 99% B; 30 min, 99%B; 36 min, 30% B |
| Flow Rate: | 0.2 ml/min |
| Solvent A: | 40% water/60% acetonitrile; 0.1% formic acid; 10 mM ammonium formate |
| Solvent B: | 90% isopropanol/10% acetonitrile; 0.1% formic acid; 10 mM ammonium formate |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS005253 |
| Analysis ID: | AN005528 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Ion trap |
| MS Type: | ESI |
| MS Comments: | El-MAVEN |
| Ion Mode: | POSITIVE |
