ArticleThe Journal of clinical investigation2020
Hepatic Slug epigenetically promotes liver lipogenesis, fatty liver disease, and type 2 diabetes.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- SNAI2/SLUG: a key regulator of endothelial-to-mesenchymal transition and vascular remodeling in cardiovascular diseases.Journal of cardiothoracic surgery · 2026Review
- Epigenetically silenced KAT2B suppresses de novo lipogenesis through destroying HDAC5/LSD1 complex assembly in renal cell carcinoma.Journal of advanced research · 2026Article
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- METTL14-Induced MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Copy number amplification of FLAD1 promotes the progression of triple-negative breast cancer through lipid metabolism.Nature communications · 2025Article
- Mechanism of Metabolic Dysfunction-associated Steatotic Liver Disease: Important role of lipid metabolism.Journal of clinical and translational hepatology · 2024Review
- Epithelial-mesenchymal transition in tissue repair and degeneration.Nature reviews. Molecular cell biology · 2024Review
- Hepatic Snai1 and Snai2 promote liver regeneration and suppress liver fibrosis in mice.Cell reports · 2024Article
- Surplus fatty acid synthesis increases oxidative stress in adipocytes and lnduces lipodystrophy.Nature communications · 2024Article
- Article
- OVOL2: an epithelial lineage determiner with emerging roles in energy homeostasis.Trends in cell biology · 2023Review
- Histone Modifications in NAFLD: Mechanisms and Potential Therapy.International journal of molecular sciences · 2023Review
- TRIM21 ameliorates hepatic glucose and lipid metabolic disorders in type 2 diabetes mellitus by ubiquitination of PEPCK1 and FASN.Cellular and molecular life sciences : CMLS · 2023Article
- Hormonal regulation of metabolism-recent lessons learned from insulin and estrogen.Clinical science (London, England : 1979) · 2023Review
- LepRb+ cell-specific deletion of Slug mitigates obesity and nonalcoholic fatty liver disease in mice.The Journal of clinical investigation · 2023Article
- Article
- Promising therapeutic aspects in human genetic imprinting disorders.Clinical epigenetics · 2022Review
- Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis.Annual review of nutrition · 2022Review
- Identifying potential regulators of JAGGED1 expression in portal mesenchymal cells.BMC research notes · 2022Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
De novo lipogenesis is tightly regulated by insulin and nutritional signals to maintain metabolic homeostasis. Excessive lipogenesis induces lipotoxicity, leading to nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes. Genetic lipogenic programs have been extensively investigated, but epigenetic regulation of lipogenesis is poorly understood. Here, we identified Slug as an important epigenetic regulator of lipogenesis. Hepatic Slug levels were markedly upregulated in mice by either feeding or insulin treatment. In primary hepatocytes, insulin stimulation increased Slug expression, stability, and interactions with epigenetic enzyme lysine-specific demethylase-1 (Lsd1). Slug bound to the fatty acid synthase (Fasn) promoter where Slug-associated Lsd1 catalyzed H3K9 demethylation, thereby stimulating Fasn expression and lipogenesis. Ablation of Slug blunted insulin-stimulated lipogenesis. Conversely, overexpression of Slug, but not a Lsd1 binding-defective Slug mutant, stimulated Fasn expression and lipogenesis. Lsd1 inhibitor treatment also blocked Slug-stimulated lipogenesis. Remarkably, hepatocyte-specific deletion of Slug inhibited the hepatic lipogenic program and protected against obesity-associated NAFLD, insulin resistance, and glucose intolerance in mice. Conversely, liver-restricted overexpression of Slug, but not the Lsd1 binding-defective Slug mutant, had the opposite effects. These results unveil an insulin/Slug/Lsd1/H3K9 demethylation lipogenic pathway that promotes NAFLD and type 2 diabetes.
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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.