ArticleNature communications2016
Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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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.
The trial behind it
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
68 citing papers in PubMed, 113 citations in OpenAlex.
- Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis.Diabetologia · 2026Review
- A pan-tissue multi-omics resource atlas of coordinated immune, metabolic, and fibrotic alterations in diet-induced MASH.iScience · 2026Article
- Induced Pluripotent Stem Cell-Derived Hepatocytes From Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease Exhibit Early Mitochondrial Dysfunction.Cellular and molecular gastroenterology and hepatology · 2026Article
- Patient-specific modeling identifies metabolic interventions for reversing glucose use reprogramming in alcohol-associated hepatitis.Communications biology · 2026Article
- Myeloid Mas drives pyruvate kinase M2-mediated Spi1 lactylation to fuel inflammatory senescence in MASLD.Signal transduction and targeted therapy · 2026Article
- Review
- MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025Review
- Hepatic Insulin Resistance and Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease: New Insights into Mechanisms and Clinical Implications.Diabetes & metabolism journal · 2025Review
- Small Extracellular Vesicle-Derived Nicotinamide Phosphoribosyltransferase (NAMPT) Induces Acyl-Coenzyme A Synthetase SLC27A4-Mediated Glycolysis to Promote Hepatocellular Carcinoma.Journal of extracellular vesicles · 2025Article
- Hepatic glucose production rises with the histological severity of metabolic dysfunction-associated steatohepatitis.Cell reports. Medicine · 2024Article
- Genome-scale metabolic network of human carotid plaque reveals the pivotal role of glutamine/glutamate metabolism in macrophage modulating plaque inflammation and vulnerability.Cardiovascular diabetology · 2024Article
- Hepatic glucose metabolism in the steatotic liver.Nature reviews. Gastroenterology & hepatology · 2024Review
- Gentiopicroside improves non-alcoholic steatohepatitis by activating PPARα and suppressing HIF1.Frontiers in pharmacology · 2024Article
- Hyperglucagonaemia and amino acid alterations in individuals with type 2 diabetes and non-alcoholic fatty liver disease.Endocrine connections · 2024Article
- Dietary Regulation of Hepatic Triacylglycerol Content-the Role of Eucaloric Carbohydrate Restriction with Fat or Protein Replacement.Advances in nutrition (Bethesda, Md.) · 2023Review
- Integrating Omics Data in Genome-Scale Metabolic Modeling: A Methodological Perspective for Precision Medicine.Metabolites · 2023Review
- Persistent fasting lipogenesis links impaired ketogenesis with citrate synthesis in humans with nonalcoholic fatty liver.The Journal of clinical investigation · 2023Observational
- Electroacupuncture treatment ameliorates metabolic disorders in obese ZDF rats by regulating liver energy metabolism and gut microbiota.Frontiers in endocrinology · 2023Article
- Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation of Glutathione Metabolism in Livers from Patients with Alcoholic Hepatitis.Metabolites · 2022Article
- Reconstructed Genome-Scale Metabolic Model Characterizes Adaptive Metabolic Flux Changes in Peripheral Blood Mononuclear Cells in Severe COVID-19 Patients.International journal of molecular sciences · 2022Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD.
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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.