ArticleDiabetologia2012
Inhibition of acetyl-CoA carboxylase 2 enhances skeletal muscle fatty acid oxidation and improves whole-body glucose homeostasis in db/db mice.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Decreasing the rate of metabolic ketone reduction in the discovery of a clinical acetyl-CoA carboxylase inhibitor for the treatment of diabetes.Journal of medicinal chemistry · 2014Trial
- Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans.The Journal of physiology · 2013Trial
- Unrestrained fatty acid oxidation triggers heart failure in mice via cardiolipin loss and mitochondrial dysfunction.The Journal of clinical investigation · 2026Article
- Unrestrained fatty acid oxidation triggers heart failure in mice via cardiolipin loss and mitochondrial dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Genetic deletion or pharmacological inhibition of acetyl-CoA carboxylase 2 enhances fatty acid oxidation and improves cardiac function and survival in the murine ATGL knockout model of severe heart failure.Journal of molecular and cellular cardiology plus · 2025Article
- Lipid droplet formation induced by icaritin derivative IC2 promotes a combination strategy for cancer therapy.Chinese medicine · 2024Article
- Pharmacologic inhibition of lipogenesis for the treatment of NAFLD.Journal of hepatology · 2024Review
- Mitochondrial fatty acid beta-oxidation: a possible therapeutic target for skeletal muscle lipotoxicity in peripheral artery disease myopathy.EXCLI journal · 2024Review
- Assessment of ACC and P450 Genes Expression in Wild Oat (Avena ludoviciana) in Different Tissues Under Herbicide Application.Biochemical genetics · 2023Article
- Lipogenesis inhibitors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2022Review
- Camphene Attenuates Skeletal Muscle Atrophy by Regulating Oxidative Stress and Lipid Metabolism in Rats.Nutrients · 2020Article
- Inhibition of acetyl-CoA carboxylase by PP-7a exerts beneficial effects on metabolic dysregulation in a mouse model of diet-induced obesity.Experimental and therapeutic medicine · 2020Article
- Metabolic-sensing of the skeletal muscle clock coordinates fuel oxidation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- WWOX somatic ablation in skeletal muscles alters glucose metabolism.Molecular metabolism · 2019Article
- Resistance determination of the ACCase-inhibiting herbicide of clodinafop propargyl in Avena ludoviciana (Durieu), and study of their interaction using molecular docking and simulation.Molecular biology reports · 2019Article
- Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Minimal impact of age and housing temperature on the metabolic phenotype of Acc2-/- mice.The Journal of endocrinology · 2016Article
- The hepatic cannabinoid 1 receptor as a modulator of hepatic energy state and food intake.British journal of clinical pharmacology · 2014Review
- Biochemical competition makes fatty-acid β-oxidation vulnerable to substrate overload.PLoS computational biology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisExcessive ectopic lipid deposition contributes to impaired insulin action in peripheral tissues and is considered an important link between obesity and type 2 diabetes mellitus. Acetyl-CoA carboxylase 2 (ACC2) is a key regulatory enzyme controlling skeletal muscle mitochondrial fatty acid oxidation; inhibition of ACC2 results in enhanced oxidation of lipids. Several mouse models lacking functional ACC2 have been reported in the literature. However, the phenotypes of the different models are inconclusive with respect to glucose homeostasis and protection from diet-induced obesity.
methodsHere, we studied the effects of pharmacological inhibition of ACC2 using as a selective inhibitor the S enantiomer of compound 9c ([S]-9c). Selectivity was confirmed in biochemical assays using purified human ACC1 and ACC2.
results(S)-9c significantly increased fatty acid oxidation in isolated extensor digitorum longus muscle from different mouse models (EC(50) 226 nmol/l). Accordingly, short-term treatment of mice with (S)-9c decreased malonyl-CoA levels in skeletal muscle and concomitantly reduced intramyocellular lipid levels. Treatment of db/db mice for 70 days with (S)-9c (10 and 30 mg/kg, by oral gavage) resulted in improved oral glucose tolerance (AUC -36%, p < 0.05), enhanced skeletal muscle 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake, as well as lowered prandial glucose (-31%, p < 0.01) and HbA(1c) (-0.7%, p < 0.05). Body weight, liver triacylglycerol, plasma insulin and pancreatic insulin content were unaffected by the treatment. CONCLUSIONS/
interpretationIn conclusion, the ACC2-selective inhibitor (S)-9c revealed glucose-lowering effects in a mouse model of diabetes mellitus.
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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.