ArticleCell death and differentiation2020
Inhibition of the mitochondrial citrate carrier, Slc25a1, reverts steatosis, glucose intolerance, and inflammation in preclinical models of NAFLD/NASH.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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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.
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Who cites it
76 citing papers in PubMed, 127 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
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- SLC25A1 drives lipid metabolic reprogramming promoting liver injury leading to hepatocellular carcinoma.Molecular biology reports · 2026Article
- Substrate supply, compartmentation, and utilization in hepatic de novo lipogenesis.Trends in endocrinology and metabolism: TEM · 2026Review
- Technology-enabled insights into SLC transporters in MAFLD: redefining the multi-hit pathogenesis and therapeutic landscape.Acta pharmacologica Sinica · 2026Review
- SLC25A1 upregulation promotes HNSCC cisplatin resistance via H3K27ac-mediated cellular senescence.NPJ precision oncology · 2026Article
- PRMT3-mediated post-translational adaptation to fasting regulates metabolic flexibility.Nature communications · 2026Article
- SLC25A1-Mediated Cholesterol Accumulation Promotes Endometriosis Progression by Enhancing Endometrial Stromal Cell Proliferation, Invasion, and M2 Macrophage Polarization.International journal of biological sciences · 2026Article
- Characterization of Visceral Adipose Tissue Proteome Reveals Metabolic Changes and Inflammatory Signatures in Severe Obesity.Obesity (Silver Spring, Md.) · 2026Article
- Exploring the significance of fatty acid metabolism reprogramming in the pathogenesis of cancer and anticancer therapy.Annals of medicine · 2025Review
- Lipid Metabolism-Signaling Crosstalk in Metabolic Disease and Aging: Mechanisms and Therapeutic Targets.Nutrients · 2025Review
- The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer.Nature communications · 2025Article
- Targeting mitochondrial transporters and metabolic reprogramming for disease treatment.Journal of translational medicine · 2025Review
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Article
- Article
- Inactivation of the SLC25A1 gene during embryogenesis induces a unique senescence program controlled by p53.Cell death and differentiation · 2025Article
- Chikungunya Replication and Infection Is Dependent upon and Alters Cellular Hexosylceramide Levels in Vero Cells.Viruses · 2025Article
- The Role of Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis.Journal of clinical and translational hepatology · 2025Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 1 institution in 2 countries.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) and its evolution to inflammatory steatohepatitis (NASH) are the most common causes of chronic liver damage and transplantation that are reaching epidemic proportions due to the upraising incidence of metabolic syndrome, obesity, and diabetes. Currently, there is no approved treatment for NASH. The mitochondrial citrate carrier, Slc25a1, has been proposed to play an important role in lipid metabolism, suggesting a potential role for this protein in the pathogenesis of this disease. Here, we show that Slc25a1 inhibition with a specific inhibitor compound, CTPI-2, halts salient alterations of NASH reverting steatosis, preventing the evolution to steatohepatitis, reducing inflammatory macrophage infiltration in the liver and adipose tissue, while starkly mitigating obesity induced by a high-fat diet. These effects are differentially recapitulated by a global ablation of one copy of the Slc25a1 gene or by a liver-targeted Slc25a1 knockout, which unravel dose-dependent and tissue-specific functions of this protein. Mechanistically, through citrate-dependent activities, Slc25a1 inhibition rewires the lipogenic program, blunts signaling from peroxisome proliferator-activated receptor gamma, a key regulator of glucose and lipid metabolism, and inhibits the expression of gluconeogenic genes. The combination of these activities leads not only to inhibition of lipid anabolic processes, but also to a normalization of hyperglycemia and glucose intolerance as well. In summary, our data show for the first time that Slc25a1 serves as an important player in the pathogenesis of fatty liver disease and thus, provides a potentially exploitable and novel therapeutic target.
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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 OpenQuestion graph.