ArticleGut2018
CPT2 downregulation adapts HCC to lipid-rich environment and promotes carcinogenesis via acylcarnitine accumulation in obesity.
Article in Gut, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
147 citing papers in PubMed, 216 citations in OpenAlex.
- Trial
- Epithelial SLC25A20 Deficiency Drives Immunosuppressive Neutrophil Remodeling via ARG1 Palmitoylation to Promote Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A covalent PFKL activator suppresses tumor growth.Nature chemical biology · 2026Article
- Germline mutations and somatic mosaicism in steatotic liver diseases and related liver carcinogenesis.Nature reviews. Gastroenterology & hepatology · 2026Review
- Contrast-enhanced MRI for identifying the steatohepatitic hepatocellular carcinoma from small hepatocellular carcinoma.Abdominal radiology (New York) · 2026Article
- MAFF regulates ferroptotic sensitivity through iron homeostasis and fatty acid synthesis.Cell death & disease · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- OCTN2 Activates a Non-Canonical Carnitine Metabolic Pathway to Promote MASH-HCC Progression and Immunotherapy Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Lipids grease the chain of cancer progression.Trends in cancer · 2026Review
- Review
- Multi-Modal Metabolomics Deciphers Pan-Cancer Metabolic Landscapes and Spatial-Niche-Specific Alternations.Metabolites · 2026Article
- Reprogrammed Lipid Metabolism as a Gatekeeper of Hepatocarcinogenesis: from Enzyme Regulation to Precision Therapy.Current oncology reports · 2026Review
- Research Communication: Serum Metabolomic Signatures Predict Tumour Recurrence After Resection or Ablation in Patients With Early-Stage Hepatocellular Carcinoma.Alimentary pharmacology & therapeutics · 2026Article
- Machine learning-based identification of targeted metabolomic biomarkers for early diagnosis and fibrosis-stage discrimination in metabolic dysfunction-associated steatotic liver disease.Frontiers in nutrition · 2026Article
- Article
- Beyond the convergence of metabolic reprogramming in primary liver cancer: a comprehensive review on energy and lipids metabolism.Frontiers in cell and developmental biology · 2026Review
- Disulfidptosis: A Metabolic Cell Death Mechanism with Therapeutic Potential in Cancer.Oncology research · 2026Review
- Untargeted Metabolomics Reveals Metabolic Reprogramming Linked to HCC Risk in Late Diagnosed Tyrosinemia Type 1.Metabolites · 2025Article
- Review
87 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
22 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveMetabolic reprogramming of tumour cells that allows for adaptation to their local environment is a hallmark of cancer. Interestingly, obesity-driven and non-alcoholic steatohepatitis (NASH)-driven hepatocellular carcinoma (HCC) mouse models commonly exhibit strong steatosis in tumour cells as seen in human steatohepatitic HCC (SH-HCC), which may reflect a characteristic metabolic alteration.
designNon-tumour and HCC tissues obtained from diethylnitrosamine-injected mice fed either a normal or a high-fat diet (HFD) were subjected to comprehensive metabolome analysis, and the significance of obesity-mediated metabolic alteration in hepatocarcinogenesis was evaluated.
resultsThe extensive accumulation of acylcarnitine species was seen in HCC tissues and in the serum of HFD-fed mice. A similar increase was found in the serum of patients with NASH-HCC. The accumulation of acylcarnitine could be attributed to the downregulation of carnitine palmitoyltransferase 2 (CPT2), which was also seen in human SH-HCC. CPT2 downregulation induced the suppression of fatty acid β-oxidation, which would account for the steatotic changes in HCC. CPT2 knockdown in HCC cells resulted in their resistance to lipotoxicity by inhibiting the Src-mediated JNK activation. Additionally, oleoylcarnitine enhanced sphere formation by HCC cells via STAT3 activation, suggesting that acylcarnitine accumulation was a surrogate marker of CPT2 downregulation and directly contributed to hepatocarcinogenesis. HFD feeding and carnitine supplementation synergistically enhanced HCC development accompanied by acylcarnitine accumulation in vivo.
conclusionIn obesity-driven and NASH-driven HCC, metabolic reprogramming mediated by the downregulation of CPT2 enables HCC cells to escape lipotoxicity and promotes hepatocarcinogenesis.
Indexed as
Identifiers
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.