ArticleHepatology (Baltimore, Md.)2018
Acetyl-CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04395950 (A Phase 1B, Single-Blinded, Linear Two Period, Placebo-controlled Study to Evaluate the Effects of 10 mg/Day of PF-05221304, Liver Targeted Acetyl-CoA Carboxylase Inhibitor), which is not on this map. Cited by 134 papers, 1 of them a synthesis that pooled it.
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.
A Phase 1B, Single-Blinded, Linear Two Period, Placebo-controlled Study to Evaluate the Effects of 10 mg/Day of PF-05221304, Liver Targeted Acetyl-CoA Carboxylase Inhibitor (ACCi) on Very Low Density Lipoprotein ApoB100 and TG Secretion
Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 249 citations in OpenAlex.
- Phytotherapy as Multi-Hit Therapy to Confront the Multiple Pathophysiology in Non-Alcoholic Fatty Liver Disease: A Systematic Review of Experimental Interventions.Medicina (Kaunas, Lithuania) · 2021Pooled it
- SomaLogic proteomics reveals new biomarkers and provides mechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH).Scientific reports · 2024Trial
- ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials.Nature medicine · 2021Trial
- Inhibition of fatty acid synthase with FT-4101 safely reduces hepatic de novo lipogenesis and steatosis in obese subjects with non-alcoholic fatty liver disease: Results from two early-phase randomized trials.Diabetes, obesity & metabolism · 2021Trial
- Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Liver-Targeting Acetyl-CoA Carboxylase Inhibitor (PF-05221304): A Three-Part Randomized Phase 1 Study.Clinical pharmacology in drug development · 2020Trial
- GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic Fatty Liver Disease.Gastroenterology · 2018Trial
- Conversion of Omega-6 to Omega-3 Fatty Acids Protects Against Liver Injury in a Murine Model.The Journal of surgical research · 2026Article
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders.Science advances · 2026Article
- AI digital pathology as a key tool providing in-depth understanding of the progression and regression of MASH and fibrosis in male mouse models.Nature communications · 2026Article
- Therapeutic targets for metabolic dysfunction-associated steatohepatitis: a personalized approach to disease management.Nature reviews. Gastroenterology & hepatology · 2026Review
- Fatty Acid Metabolism in Health and Cancer: From Fundamental Mechanisms to Therapeutic Application.MedComm · 2026Review
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- Targeting the LPI/GPR55 Axis in MAFLD and MASH: Novel Insights, Therapeutic Strategies and Future Directions.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Long-Term Fructose Intake Induces Moderate Liver Inflammation but Does not Overlap with the Detrimental Effects of the Ketogenic Diet on Hepatic Steatosis in Rats.Inflammation · 2026Article
- Review
- TSP50 attenuates metabolic dysfunction-associated steatotic liver disease via SCD1 degradation-mediated suppression of hepatocyte lipogenesis.Cellular & molecular biology letters · 2026Article
- Hyperoside modulates bile acid and fatty acid metabolism, presenting a potentially promising treatment for non-alcoholic fatty liver disease.Journal of advanced research · 2026Article
- The role of lysine acylation in metabolic dysregulation and inflammatory responses within the hepatic immune microenvironment of MASLD.Frontiers in immunology · 2026Review
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
74 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Pharmacologic inhibition of acetyl-CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for nonalcoholic fatty liver disease (NAFLD) through simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation. However, the effects of ACC inhibition on hepatic mitochondrial oxidation, anaplerosis, and ketogenesis in vivo are unknown. Here, we evaluated the effect of a liver-directed allosteric inhibitor of ACC1 and ACC2 (Compound 1) on these parameters, as well as glucose and lipid metabolism, in control and diet-induced rodent models of NAFLD. Oral administration of Compound 1 preferentially inhibited ACC enzymatic activity in the liver, reduced hepatic malonyl-CoA levels, and enhanced hepatic ketogenesis by 50%. Furthermore, administration for 6 days to high-fructose-fed rats resulted in a 20% reduction in hepatic de novo lipogenesis. Importantly, long-term treatment (21 days) significantly reduced high-fat sucrose diet-induced hepatic steatosis, protein kinase C epsilon activation, and hepatic insulin resistance. ACCi treatment was associated with a significant increase in plasma triglycerides (approximately 30% to 130%, depending on the length of fasting). ACCi-mediated hypertriglyceridemia could be attributed to approximately a 15% increase in hepatic very low-density lipoprotein production and approximately a 20% reduction in triglyceride clearance by lipoprotein lipase (P ≤ 0.05). At the molecular level, these changes were associated with increases in liver X receptor/sterol response element-binding protein-1 and decreases in peroxisome proliferator-activated receptor-α target activation and could be reversed with fenofibrate co-treatment in a high-fat diet mouse model. Conclusion: Collectively, these studies warrant further investigation into the therapeutic utility of liver-directed ACC inhibition for the treatment of NAFLD and hepatic insulin resistance.
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.