ArticleJournal of lipid research2012
Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver.
Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03480594 (Effect of Fatty Liver on TCA Cycle Flux and the Pentose Phosphate Pathway), which is not on this map. Cited by 239 papers, 1 of them a synthesis that pooled it.
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.
Effect of Fatty Liver on TCA Cycle Flux and the Pentose Phosphate Pathway (HP FFF)
Who cites it
239 citing papers in PubMed, 1 synthesis or guideline pooled it, 400 citations in OpenAlex.
- Association between obstructive sleep apnea and non-alcoholic fatty liver disease: a systematic review and meta-analysis.Sleep & breathing = Schlaf & Atmung · 2018Pooled it
- Microvesicles Correlated with Components of Metabolic Syndrome in Men with Type 2 Diabetes Mellitus and Lowered Testosterone Levels But Were Unaltered by Testosterone Therapy.Journal of diabetes research · 2017Trial
- The Gibbs free energy landscape based on liver metabolome revealed thermodynamic robustness against fasting and obesity.iScience · 2026Article
- Biliverdin reductase A deficiency reveals sex- and brain region-specific vulnerability to high-fat diet feeding.Redox biology · 2026Article
- Chronic choline restriction remodels hepatic lipid metabolism and drives insulin resistance through a CD36-ETNPPL regulatory axis.Molecular metabolism · 2026Article
- Circulating β-Hydroxybutyrate in Glycemic Progression and Diabetic Cardiomyopathy: Adaptive Signal or Maladaptive Substrate?International journal of molecular sciences · 2026Review
- Endurance exercise elicits temporal and sexual dimorphic multi-omics remodeling of liver metabolism revealed by MoTrPAC.Cell reports · 2026Article
- Natural Plant-Derived Compounds Targeting Oxidative Stress and Inflammation in NAFLD-Mechanisms and Repositioning Potential.Current issues in molecular biology · 2026Review
- Serum metabolomics of diabetic dogs treated with daily administration of a commercially available lyophilized feces preparation.Veterinary research communications · 2026Article
- Comparative urinary metabolomics reveals unique and shared pathways in COVID-19 and liver diseases.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- The impact of lipid-rich nutrition on ketogenesis and muscle weakness in sepsis.Intensive care medicine experimental · 2026Article
- Preliminary metabolic characterization of hepatic lipidosis in cats using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry: pathway insights and candidate biomarkers.Journal of veterinary internal medicine · 2026Article
- Sarco/Endoplasmic Reticulum CaJournal of the American Heart Association · 2026Article
- Viral manipulation of host cell glutamine metabolism and glutamine rewiring in hepatic diseases: Editorial on "Glutamate dehydrogenase 1-dependent α-ketoglutarate promotes hepatitis B virus transcription by modulating histone methylations on the covalently closed circular DNA minichromosome".Clinical and molecular hepatology · 2026Article
- Association between ketone body levels and chronic liver disease: Epidemiological studies and potential mechanisms.AIMS public health · 2026Review
- Maternal postpartum sedentary life exacerbates the metabolic impact of moderately fat-rich diet in male mice.npj metabolic health and disease · 2025Article
- Reduced liver mitochondrial energy metabolism impairs food intake regulation following gastric preloads and fasting.Molecular metabolism · 2025Article
- Interaction Between Rumen Microbiota and Epithelial Mitochondrial Dynamics in Tibetan Sheep: Elucidating the Mechanism of Rumen Epithelial Energy Metabolism.Biotech (Basel (Switzerland)) · 2025Article
- Loss of ovarian function prevents exercise-induced activation of hepatic mitophagic flux.American journal of physiology. Endocrinology and metabolism · 2025Article
- Induction of Fructose Mediated De Novo Lipogenesis Coexists with the Upregulation of Mitochondrial Oxidative Function in Mice Livers.The Journal of nutrition · 2025Article
179 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The manner in which insulin resistance impinges on hepatic mitochondrial function is complex. Although liver insulin resistance is associated with respiratory dysfunction, the effect on fat oxidation remains controversial, and biosynthetic pathways that traverse mitochondria are actually increased. The tricarboxylic acid (TCA) cycle is the site of terminal fat oxidation, chief source of electrons for respiration, and a metabolic progenitor of gluconeogenesis. Therefore, we tested whether insulin resistance promotes hepatic TCA cycle flux in mice progressing to insulin resistance and fatty liver on a high-fat diet (HFD) for 32 weeks using standard biomolecular and in vivo (2)H/(13)C tracer methods. Relative mitochondrial content increased, but respiratory efficiency declined by 32 weeks of HFD. Fasting ketogenesis became unresponsive to feeding or insulin clamp, indicating blunted but constitutively active mitochondrial β-oxidation. Impaired insulin signaling was marked by elevated in vivo gluconeogenesis and anaplerotic and oxidative TCA cycle flux. The induction of TCA cycle function corresponded to the development of mitochondrial respiratory dysfunction, hepatic oxidative stress, and inflammation. Thus, the hepatic TCA cycle appears to enable mitochondrial dysfunction during insulin resistance by increasing electron deposition into an inefficient respiratory chain prone to reactive oxygen species production and by providing mitochondria-derived substrate for elevated gluconeogenesis.
Indexed as
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What OpenQuestion holds
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.