ArticleJCI insight2023
Hepatic FASN deficiency differentially affects nonalcoholic fatty liver disease and diabetes in mouse obesity models.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Periportal hepatocytes secret SAA1 to recruit MoKCs and interactions through CADM1 signaling to promote MASLD.Hepatology international · 2026Article
- Hepatic glutathione depletion ameliorates MASLD through selective protein oxidation and inhibition of lipogenesis.The Journal of clinical investigation · 2026Article
- Ufmylation-Deficient DDRGK1 Ameliorates Obesity by Inhibiting FASN-Mediated Adipocyte Lipogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The implications of FASN in viral infection and related diseases: a promising target in antiviral therapies.Frontiers in cellular and infection microbiology · 2026Review
- A novel LepR knockout hamster model for type 2 diabetes and its complications: a complementary platform to conventional rodent models.Frontiers in endocrinology · 2026Article
- Multimorbidity and animal models.Animal models and experimental medicine · 2025Review
- Combined nicotinamide riboside and magnesium-l-theanine protects against chronic stress-induced gut-liver injury by modulating NAD⁺ and metabolic pathways.Molecular biology reports · 2025Article
- SUV39H1 facilitate the osteogenic differentiation of dental pulp stem cells by modulating lipid metabolism and mitochondrial dynamics through FASN via non-histone methylation and ubiquitination mechanism.Stem cell research & therapy · 2025Article
- Antifibrotic therapies for metabolic dysfunction-associated steatotic liver disease.JHEP reports : innovation in hepatology · 2025Review
- Pharmacological Treatment of MASLD: Contemporary Treatment and Future Perspectives.International journal of molecular sciences · 2025Review
- Goat Whey Protein Hydrolysate Mitigates High-Fructose Corn Syrup-Induced Hepatic Steatosis in a Murine Model.Nutrients · 2025Article
- Effect of dolutegravir-based antiretroviral therapy on glycemic control in female mice.Scientific reports · 2025Article
- Baihu Jia Renshen Decoction may improve skeletal muscle and adipose tissue functions of type I diabetic rats by affecting pancreatic β-cell function.Genes & genomics · 2025Article
- The Role of microRNA-22 in Metabolism.International journal of molecular sciences · 2025Review
- Abnormal ac4C modification in metabolic dysfunction associated steatotic liver cells.Scientific reports · 2025Article
- Unveiling the molecular mechanisms of stigmasterol on diabetic retinopathy: BNM framework construction and experimental validation.Frontiers in medicine · 2025Article
- The effects of coconut oil intake on metabolic disorders and fatty liver disease in mice.Journal of nutritional science · 2025Article
- Metabolism of hepatic stellate cells in chronic liver diseases: emerging molecular and therapeutic interventions.Theranostics · 2025Review
- Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: primary and secondary gene responses with links to disease progression.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Low-Iron Diet-Induced Fatty Liver Development Is Microbiota Dependent and Exacerbated by Loss of the Mitochondrial Iron Importer Mitoferrin2.Nutrients · 2024Article
Corrections and comments
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Authors and funding
32 authors at 19 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes are interacting comorbidities of obesity, and increased hepatic de novo lipogenesis (DNL), driven by hyperinsulinemia and carbohydrate overload, contributes to their pathogenesis. Fatty acid synthase (FASN), a key enzyme of hepatic DNL, is upregulated in association with insulin resistance. However, the therapeutic potential of targeting FASN in hepatocytes for obesity-associated metabolic diseases is unknown. Here, we show that hepatic FASN deficiency differentially affects NAFLD and diabetes depending on the etiology of obesity. Hepatocyte-specific ablation of FASN ameliorated NAFLD and diabetes in melanocortin 4 receptor-deficient mice but not in mice with diet-induced obesity. In leptin-deficient mice, FASN ablation alleviated hepatic steatosis and improved glucose tolerance but exacerbated fed hyperglycemia and liver dysfunction. The beneficial effects of hepatic FASN deficiency on NAFLD and glucose metabolism were associated with suppression of DNL and attenuation of gluconeogenesis and fatty acid oxidation, respectively. The exacerbation of fed hyperglycemia by FASN ablation in leptin-deficient mice appeared attributable to impairment of hepatic glucose uptake triggered by glycogen accumulation and citrate-mediated inhibition of glycolysis. Further investigation of the therapeutic potential of hepatic FASN inhibition for NAFLD and diabetes in humans should thus consider the etiology of obesity.
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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.