ArticleThe Biochemical journal2013
Diacylglycerol kinase θ couples farnesoid X receptor-dependent bile acid signalling to Akt activation and glucose homoeostasis in hepatocytes.
Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- DGKs in lipid signaling and disease intervention: structural basis, pathological mechanisms, and emerging therapeutic strategies.Cellular & molecular biology letters · 2025Review
- A transcriptional evaluation of the melanoma and squamous cell carcinoma TIL compartment reveals an unexpected spectrum of exhausted and functional T cells.Frontiers in oncology · 2023Article
- Bariatric surgery for diabetic comorbidities: A focus on hepatic, cardiac and renal fibrosis.Frontiers in pharmacology · 2022Review
- Tumor Growth in the High Frequency Medulloblastoma Mouse Model Ptch1Frontiers in oncology · 2021Article
- Adipose Tissue Gene Expression Associations Reveal Hundreds of Candidate Genes for Cardiometabolic Traits.American journal of human genetics · 2019Article
- Changes in Bile Acid Metabolism, Transport, and Signaling as Central Drivers for Metabolic Improvements After Bariatric Surgery.Current obesity reports · 2019Review
- Bile acid metabolism regulated by the gut microbiota promotes non-alcoholic steatohepatitis-associated hepatocellular carcinoma in mice.Oncotarget · 2018Article
- Establishment of a novel hepatic steatosis cell model by Cas9/sgRNA-mediated DGKθ gene knockout.Molecular medicine reports · 2018Article
- Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases.Cell metabolism · 2018Review
- Potential Nexus of Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Insulin Resistance Between Hepatic and Peripheral Tissues.Frontiers in pharmacology · 2018Review
- Glucagon and Insulin Cooperatively Stimulate Fibroblast Growth Factor 21 Gene Transcription by Increasing the Expression of Activating Transcription Factor 4.The Journal of biological chemistry · 2017Article
- A novel diacylglycerol kinase α-selective inhibitor, CU-3, induces cancer cell apoptosis and enhances immune response.Journal of lipid research · 2016Article
- mRNA expression of diacylglycerol kinase isoforms in insulin-sensitive tissues: effects of obesity and insulin resistance.Physiological reports · 2015Article
- Silencing diacylglycerol kinase-theta expression reduces steroid hormone biosynthesis and cholesterol metabolism in human adrenocortical cells.Biochimica et biophysica acta · 2014Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
DGKs (diacylglycerol kinases) catalyse the conversion of diacylglycerol into PA (phosphatidic acid), a positive modulator of mTOR (mammalian target of rapamycin). We have found that chenodeoxycholic acid and the synthetic FXR (farnesoid X receptor) ligand GW4064 induce the mRNA and protein expression of DGKθ in the HepG2 cell line and in primary human hepatocytes. Reporter gene studies using 1.5 kB of the DGKθ promoter fused to the luciferase gene revealed that bile acids increase DGKθ transcriptional activity. Mutation of putative FXR-binding sites attenuated the ability of GW4046 to increase DGKθ luciferase activity. Consistent with this finding, ChIP (chromatin immunoprecipitation) assays demonstrated that bile acid signalling increased the recruitment of FXR to the DGKθ promoter. Furthermore, GW4064 evoked a time-dependent increase in the cellular concentration of PA. We also found that GW4064 and PA promote the phosphorylation of mTOR, Akt and FoxO1 (forkhead box O1), and that silencing DGKθ expression significantly abrogated the ability of GW4046 to promote the phosphorylation of these PA-regulated targets. DGKθ was also required for bile-acid-dependent decreased glucose production. Taken together, our results establish DGKθ as a key mediator of bile-acid-stimulated modulation of mTORC2 (mTOR complex 2), the Akt pathway and glucose homoeostasis.
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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.