ReviewMolecular metabolism2021
Therapeutic potential of mitochondrial uncouplers for the treatment of metabolic associated fatty liver disease and NASH.
Review in Molecular metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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.
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Who cites it
45 citing papers in PubMed, 87 citations in OpenAlex.
- Clinical Trial: A Phase 2b Study to Evaluate the Efficacy and Safety of MK-3655 in Individuals With Pre-Cirrhotic MASH.Alimentary pharmacology & therapeutics · 2025Trial
- Fatty acid-activated proton transporter SR4 prevents hepatic steatosis and metabolic alterations in diabetic mice by improving mitochondria function, energy balance and oxidative stress.Experimental and therapeutic medicine · 2026Article
- Lipid Metabolic Disorders: a Pivotal Driver in Type 2 Diabetes Mellitus Pathogenesis.Current obesity reports · 2026Review
- Tuning the Fire: Context-Dependent Mitochondrial ROS Signaling, Mitohormesis, and Redox-Modulating Interventions.Biomolecules · 2026Review
- Incretin and Glucagon Signalling in MASLD and MASH: Integrating Metabolic Pathways With Disease Progression.Diabetes, obesity & metabolism · 2026Review
- Integrative Multiomics Analysis Reveals the Ameliorative Effects ofMolecules (Basel, Switzerland) · 2026Article
- Toward a gut-AMPK axis: the microbiome and AMPK signaling in nutrition and healthy aging.Frontiers in physiology · 2026Review
- Interaction of bile acids with functionally active liver mitochondria: uncoupling activity, detergent effect, and antioxidant action.Journal of bioenergetics and biomembranes · 2025Article
- Efficacy and safety of anti-obesity drugs in metabolic dysfunction-associated steatotic liver disease: An updated review.World journal of gastroenterology · 2025Review
- Precision Medicine: Therapeutically Targeting Mitochondrial Alterations in Heart Failure.JACC. Basic to translational science · 2025Review
- Targeting Mitochondrial Dysfunction to Prevent Endothelial Dysfunction and Atherosclerosis in Diabetes: Focus on the Novel Uncoupler BAM15.International journal of molecular sciences · 2025Review
- Nitazoxanide protects against heart failure with preserved ejection and metabolic syndrome induced by high-fat diet (HFD) plus L-NAME "two-hit" in mice.Acta pharmaceutica Sinica. B · 2025Article
- Nigericin modifies the mechanism of the uncoupling action of bile acids in rat liver mitochondria by converting ΔpH into Δψ.Journal of bioenergetics and biomembranes · 2025Article
- Altered mitochondrial function: a clue therapeutic strategies between metabolic dysfunction-associated steatotic liver disease and chronic kidney disease?Frontiers in nutrition · 2025Review
- Paradigm shift in obesity treatment: an extensive review of current pipeline agents.Turkish journal of medical sciences · 2025Review
- Recent development of mitochondrial metabolism and dysfunction in osteoarthritis.Frontiers in pharmacology · 2025Review
- Targeting the AMP-activated protein kinase pathway: the active metabolites of botanical drugs represent potential strategies for treating metabolic-associated fatty liver disease.Frontiers in pharmacology · 2025Review
- Design, synthesis, and biological evaluation of imidazo[4,5-b]pyridine mitochondrial uncouplers for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).European journal of medicinal chemistry · 2024Article
- Glucagon promotes increased hepatic mitochondrial oxidation and pyruvate carboxylase flux in humans with fatty liver disease.Cell metabolism · 2024Article
- Potential therapeutic strategies for MASH: from preclinical to clinical development.Life metabolism · 2024Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMitochondrial uncouplers shuttle protons across the inner mitochondrial membrane via a pathway that is independent of adenosine triphosphate (ATP) synthase, thereby uncoupling nutrient oxidation from ATP production and dissipating the proton gradient as heat. While initial toxicity concerns hindered their therapeutic development in the early 1930s, there has been increased interest in exploring the therapeutic potential of mitochondrial uncouplers for the treatment of metabolic diseases. SCOPE OF REVIEW: In this review, we cover recent advances in the mechanisms by which mitochondrial uncouplers regulate biological processes and disease, with a particular focus on metabolic associated fatty liver disease (MAFLD), nonalcoholic hepatosteatosis (NASH), insulin resistance, and type 2 diabetes (T2D). We also discuss the challenges that remain to be addressed before synthetic and natural mitochondrial uncouplers can successfully enter the clinic. MAJOR
conclusionsRodent and non-human primate studies suggest that a myriad of small molecule mitochondrial uncouplers can safely reverse MAFLD/NASH with a wide therapeutic index. Despite this, further characterization of the tissue- and cell-specific effects of mitochondrial uncouplers is needed. We propose targeting the dosing of mitochondrial uncouplers to specific tissues such as the liver and/or developing molecules with self-limiting properties to induce a subtle and sustained increase in mitochondrial inefficiency, thereby avoiding systemic toxicity concerns.
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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 Socratic graph.