ArticleCell metabolism2017
Acetyl CoA Carboxylase Inhibition Reduces Hepatic Steatosis but Elevates Plasma Triglycerides in Mice and Humans: A Bedside to Bench Investigation.
Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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 187 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.
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
187 citing papers in PubMed, 402 citations in OpenAlex.
- Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial.Cell metabolism · 2026Trial
- SomaLogic proteomics reveals new biomarkers and provides mechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH).Scientific reports · 2024Trial
- Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH.The New England journal of medicine · 2023Trial
- 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
- Insulin resistance drives hepatic de novo lipogenesis in nonalcoholic fatty liver disease.The Journal of clinical investigation · 2020Trial
- GS-0976 Reduces Hepatic Steatosis and Fibrosis Markers in Patients With Nonalcoholic Fatty Liver Disease.Gastroenterology · 2018Trial
- Navigating the potential of algal peptides: health effects, market applications, and scientific challenges.Annals of medicine · 2026Review
- Glyoxalase 1 loss reduces fatty liver but impairs glucose handling in male mice.Physiological reports · 2026Article
- A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders.Science advances · 2026Article
- Dietary Intake of 25-Hydroxy Vitamin D3 from First Feeding Improves Feed Efficiency and Modulates Hepatic Metabolic Transcriptome in Rainbow Trout.Marine biotechnology (New York, N.Y.) · 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
- Protective Effects ofAnimals : an open access journal from MDPI · 2026Article
- Substrate supply, compartmentation, and utilization in hepatic de novo lipogenesis.Trends in endocrinology and metabolism: TEM · 2026Review
- Hepatic Lipoprotein Production, Cardiometabolic Phenotypes, and Subtypes of Steatotic Liver Disease.Circulation research · 2026Review
- Transient fetal hyperglycemia reprograms adipogenesis, lipogenesis, and insulin signaling in zebrafish.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Unrestrained fatty acid oxidation triggers heart failure in mice via cardiolipin loss and mitochondrial dysfunction.The Journal of clinical investigation · 2026Article
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- Bench-to-Bedside Evaluation of Sulforaphane/BroccoMax® on Fatty Acid Synthesis in Prostate Cancer.Cancer prevention research (Philadelphia, Pa.) · 2026Article
127 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Inhibiting lipogenesis prevents hepatic steatosis in rodents with insulin resistance. To determine if reducing lipogenesis functions similarly in humans, we developed MK-4074, a liver-specific inhibitor of acetyl-CoA carboxylase (ACC1) and (ACC2), enzymes that produce malonyl-CoA for fatty acid synthesis. MK-4074 administered to subjects with hepatic steatosis for 1 month lowered lipogenesis, increased ketones, and reduced liver triglycerides by 36%. Unexpectedly, MK-4074 increased plasma triglycerides by 200%. To further investigate, mice that lack ACC1 and ACC2 in hepatocytes (ACC dLKO) were generated. Deletion of ACCs decreased polyunsaturated fatty acid (PUFA) concentrations in liver due to reduced malonyl-CoA, which is required for elongation of essential fatty acids. PUFA deficiency induced SREBP-1c, which increased GPAT1 expression and VLDL secretion. PUFA supplementation or siRNA-mediated knockdown of GPAT1 normalized plasma triglycerides. Thus, inhibiting lipogenesis in humans reduced hepatic steatosis, but inhibiting ACC resulted in hypertriglyceridemia due to activation of SREBP-1c and increased VLDL secretion.
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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.