ArticleNature communications2018
Insulin/Snail1 axis ameliorates fatty liver disease by epigenetically suppressing lipogenesis.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
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- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- Post-translational modifications in the pathophysiological process of metabolic dysfunction‑associated steatotic liver disease.Cell & bioscience · 2025Review
- METTL14-Induced MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- A tumor-secreted protein utilizes glucagon release to cause host wasting.Cell discovery · 2025Article
- Genome-Wide Profiling of H3K27ac Identifies TDO2 as a Pivotal Therapeutic Target in Metabolic Associated Steatohepatitis Liver Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Epithelial-mesenchymal transition in tissue repair and degeneration.Nature reviews. Molecular cell biology · 2024Review
- Article
- Hepatic Snai1 and Snai2 promote liver regeneration and suppress liver fibrosis in mice.Cell reports · 2024Article
- Loss ofZoological research · 2024Article
- Surplus fatty acid synthesis increases oxidative stress in adipocytes and lnduces lipodystrophy.Nature communications · 2024Article
- OVOL2: an epithelial lineage determiner with emerging roles in energy homeostasis.Trends in cell biology · 2023Review
- Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice.Nature metabolism · 2023Article
- Adipose METTL14-Elicited NAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Histone Modifications in NAFLD: Mechanisms and Potential Therapy.International journal of molecular sciences · 2023Review
- Bavachin protects against diet-induced hepatic steatosis and obesity in mice.Acta pharmacologica Sinica · 2023Article
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- The malignancy suppression and ferroptosis facilitation of BCL6 in gastric cancer mediated by FZD7 repression are strengthened by RNF180/RhoC pathway.Cell & bioscience · 2023Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Insulin stimulates lipogenesis but insulin resistance is also associated with increased hepatic lipogenesis in obesity. However, the underlying mechanism remains poorly characterized. Here, we show a noncanonical insulin-Snail1 pathway that suppresses lipogenesis. Insulin robustly upregulates zinc-finger protein Snail1 in a PI 3-kinase-dependent manner. In obesity, the hepatic insulin-Snail1 cascade is impaired due to insulin resistance. Hepatocyte-specific deletion of Snail1 enhances insulin-stimulated lipogenesis in hepatocytes, exacerbates dietary NAFLD in mice, and attenuates NAFLD-associated insulin resistance. Liver-specific overexpression of Snail1 has the opposite effect. Mechanistically, Snail1 binds to the fatty acid synthase promoter and recruits HDAC1/2 to induce deacetylation of H3K9 and H3K27, thereby repressing fatty acid synthase promoter activity. Our data suggest that insulin pathways bifurcate into canonical (lipogenic) and noncanonical (anti-lipogenesis by Snail1) two arms. The noncanonical arm counterbalances the canonical arm through Snail1-elicited epigenetic suppression of lipogenic genes. Impairment in the insulin-Snail1 arm may contribute to NAFLD in obesity.
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