ArticleEndocrinology2019
Hepatic HKDC1 Expression Contributes to Liver Metabolism.
Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 83 citations in OpenAlex.
- Lauric-acid-rich Hermetia illucens meal modulates lipid metabolism in the liver and the fatty acid profile in piglet tissues.Scientific reports · 2026Article
- Article
- HNF4α-HKDC1 axis orchestrates a metabolic rewiring to promote migration and metastasis in advanced gastric cancer.Cell death & disease · 2026Article
- Silencing of the Metabolic Gene HKDC1 Is Associated With Aging and Neurodegeneration in Mice and Humans.Aging cell · 2026Article
- Impact ofArchives of medical science : AMS · 2026Article
- Characterization and Inhibition of Human Hexokinase Domain Containing Protein 1 Reveals an Enzyme with Unique Catalytic and Regulatory Traits.ACS chemical biology · 2025Article
- Identification of Glycolysis-Related Genes in MAFLD and Their Immune Infiltration Implications: A Multi-Omics Analysis with Experimental Validation.Biomedicines · 2025Article
- Validation of signature molecular profiles of advanced HCV liver disease in hepatocellular carcinoma patients.Virus research · 2025Article
- Sustainable Utilization of Coffee Pulp, a By-Product of Coffee Production: Effects on Metabolic Syndrome in Fructose-Fed Rats.Antioxidants (Basel, Switzerland) · 2025Article
- Exploring glycolytic enzymes in disease: potential biomarkers and therapeutic targets in neurodegeneration, cancer and parasitic infections.Open biology · 2025Review
- The Counteracting Effect of Chrysin on Dietary Fructose-Induced Metabolic-Associated Fatty Liver Disease (MAFLD) in Rats with a Focus on Glucose and Lipid Metabolism.Molecules (Basel, Switzerland) · 2025Article
- HKDC1 functions as a glucose sensor and promotes metabolic adaptation and cancer growth via interaction with PHB2.Cell death and differentiation · 2024Article
- Exploring Smad5: a review to pave the way for a deeper understanding of the pathobiology of common respiratory diseases.Molecular medicine (Cambridge, Mass.) · 2024Review
- New insights into the treatment of polycystic ovary syndrome: HKDC1 promotes the growth of ovarian granulocyte cells by regulating mitochondrial function and glycolysis.Journal of molecular histology · 2024Article
- HKDC1 promotes tumor immune evasion in hepatocellular carcinoma by coupling cytoskeleton to STAT1 activation and PD-L1 expression.Nature communications · 2024Article
- HKDC1, a target of TFEB, is essential to maintain both mitochondrial and lysosomal homeostasis, preventing cellular senescence.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Proteomics identifies the developmental regulation of HKDC1 in liver of pigs and mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Cold Exposure Regulates Hepatic Glycogen and Lipid Metabolism in Newborn Goats.International journal of molecular sciences · 2023Article
- Liver-specific overexpression of HKDC1 increases hepatocyte size and proliferative capacity.Scientific reports · 2023Article
- Aiding Cancer's "Sweet Tooth": Role of Hexokinases in Metabolic Reprogramming.Life (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
Abstract
Glucokinase (GCK) is the principal hexokinase (HK) in the liver, operating as a glucose sensor to regulate glucose metabolism and lipid homeostasis. Recently, we proposed HK domain-containing 1 (HKDC1) to be a fifth HK with expression in the liver. Here, we reveal HKDC1 to have low glucose-phosphorylating ability and demonstrate its association with the mitochondria in hepatocytes. As we have shown previously that genetic deletion of HKDC1 leads to altered hepatic triglyceride levels, we also explored the influence of overexpression of HKDC1 in hepatocytes on cellular metabolism, observing reduced glycolytic capacity and maximal mitochondrial respiration with concurrent reductions in glucose oxidation and mitochondrial membrane potential. Furthermore, we found that acute in vivo overexpression of HKDC1 in the liver induced substantial changes in mitochondrial dynamics. Altogether, these findings suggest that overexpression of HKDC1 causes mitochondrial dysfunction in hepatocytes. However, its overexpression was not enough to alter energy storage in the liver but led to mild improvement in glucose tolerance. We next investigated the conditions necessary to induce HKDC1 expression, observing HKDC1 expression to be elevated in human patients whose livers were at more advanced stages of nonalcoholic fatty liver disease (NAFLD) and similarly, found high liver expression in mice on diets causing high levels of liver inflammation and fibrosis. Overall, our data suggest that HKDC1 expression in hepatocytes results in defective mitochondrial function and altered hepatocellular metabolism and speculate that its expression in the liver may play a role in the development of NAFLD.
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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.