Summary of project PR002116
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 PR002116. The data can be accessed directly via it's Project DOI: 10.21228/M83N8D This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002116 |
| Project DOI: | doi: 10.21228/M83N8D |
| Project Title: | Bempedoic acid improves diet-induced steatosis independent of hepatic ACLY |
| Project Type: | MS quantitative analysis |
| 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 PPARa (Peroxisome proliferator-activated receptor alpha) ligands and lower expression of PPARa target genes controlling fatty acid oxidation. Importantly, BPA treatment ameliorates Western diet-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 |
Summary of all studies in project PR002116
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003421 | BPA regulates the abundance of endogenous PPARa ligands and fatty acid oxidation | Mus musculus | Salk Institute for Biological Studies | MS | 2024-08-26 | 1 | 25 | Uploaded data (159.3M)* |
| ST003422 | Impact of ACLY and ACSS2 on the development of MASLD and phosphatidylcholines levels on longterm Western diet | Mus musculus | Salk Institute for Biological Studies | MS | 2024-09-10 | 1 | 36 | Uploaded data (269.5M)* |
| ST003423 | Impact of ACLY and ACSS2 on the development of MASLD on longterm Western diet | Mus musculus | Salk Institute for Biological Studies | MS | 2024-08-26 | 1 | 36 | Uploaded data (3.9G)* |
