ArticlePloS one2020
Acetyl-CoA carboxylase 1 and 2 inhibition ameliorates steatosis and hepatic fibrosis in a MC4R knockout murine model of nonalcoholic steatohepatitis.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Integrative metabolomics and malonyl-proteomics reveal the crosstalk between metabolic reprogramming and lysine malonylation in liver fibrosis.Journal of physiology and biochemistry · 2026Article
- Microalgae Oil Attenuates Liver Fat Deposition in NAFLD via Modulation of Anti-Lipogenic Genes and Insulin Signaling Pathways in HFD Mice.Food science & nutrition · 2026Article
- Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison.International journal of obesity (2005) · 2026Article
- Cross-organ multi-omics profiling of microbiome and metabolome along the gut-liver axis in MASH model mice induced by western diet and MC4R knockout.Gut pathogens · 2026Article
- Differences between therapeutic mechanisms of resmetirom and semaglutide against MASH in western diet-fed MC4R-knockout mice.Scientific reports · 2025Article
- ACC-1 as a Possible Biochemical Indicator of Lipoapoptosis in In Vivo and In Vitro Models of MAFLD.International journal of molecular sciences · 2025Article
- Hidden in the Fat: Unpacking the Metabolic Tango Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Syndrome.International journal of molecular sciences · 2025Review
- Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability.Cell metabolism · 2024Article
- Molecular cloning and gene expression of acc2 from grass carp (Ctenopharyngodon idella) and the regulation of glucose metabolism by ACCs inhibitor.Molecular biology reports · 2024Article
- Pharmacologic inhibition of lipogenesis for the treatment of NAFLD.Journal of hepatology · 2024Review
- Article
- Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Micropatterned primary hepatocyte co-culture (HEPATOPAC) for fatty liver disease modeling and drug screening.Scientific reports · 2023Article
- Uncoupling Lipid Synthesis from Adipocyte Development.Biomedicines · 2023Article
- A Review of Defatting Strategies for Non-Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2022Review
- Lipid alterations in chronic liver disease and liver cancer.JHEP reports : innovation in hepatology · 2022Review
- Lipogenesis inhibitors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2022Review
- Identification of a potent NAFLD drug candidate for controlling T2DM-mediated inflammation and secondary damageFrontiers in pharmacology · 2022Article
- Acetyl-CoA carboxylase inhibitors in non-alcoholic steatohepatitis: Is there a benefit?World journal of gastroenterology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in de novo lipogenesis, which is increased in the livers of patients with nonalcoholic steatohepatitis. GS-0976 (firsocostat), an inhibitor of isoforms ACC1 and ACC2, reduced hepatic steatosis and serum fibrosis biomarkers such as tissue inhibitor of metalloproteinase 1 in patients with nonalcoholic steatohepatitis in a randomized controlled trial, although the impact of this improvement on fibrosis has not fully been evaluated in preclinical models. Here, we used Western diet-fed melanocortin 4 receptor-deficient mice that have similar phenotypes to nonalcoholic steatohepatitis patients including progressively developed hepatic steatosis as well as fibrosis. We evaluated the effects of ACC1/2 inhibition on hepatic fibrosis. After the confirmation of significant hepatic fibrosis with a 13-week pre-feeding, GS-0976 (4 and 16 mg/kg/day) treatment for 9 weeks lowered malonyl-CoA and triglyceride content in the liver and improved steatosis, histologically. Furthermore, GS-0976 reduced the histological area of hepatic fibrosis, hydroxyproline content, mRNA expression level of type I collagen in the liver, and plasma tissue metalloproteinase inhibitor 1, suggesting an improvement of hepatic fibrosis. The treatment with GS-0976 was also accompanied by reductions of plasma ALT and AST levels. These data demonstrate that improvement of hepatic lipid metabolism by ACC1/2 inhibition could be a new option to suppress fibrosis progression as well as to improve hepatic steatosis in nonalcoholic steatohepatitis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.