ArticleGastroenterology2023
Hepatocyte Kctd17 Inhibition Ameliorates Glucose Intolerance and Hepatic Steatosis Caused by Obesity-induced Chrebp Stabilization.
Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 17 citations in OpenAlex.
- E3 Ubiquitin Ligases in MASH-Associated Liver Fibrosis: Mechanisms and Therapeutic Opportunities.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Multifaceted roles of KCTD17 in cellular homeostasis and disease.BMB reports · 2026Review
- AIBP deficiency drives MAFLD advancement via ITGβ3 mediated lipid metabolism disruption and pro-inflammatory activation.Cell communication and signaling : CCS · 2026Article
- Research progress on the mechanistic pathways and biomarkers of therapeutic drugs for metabolic-associated steatotic liver disease.Frontiers in cell and developmental biology · 2026Review
- Systematic profiling reveals hepatic immune and metabolic dysregulation in DNASE1L3-deficient mice.iScience · 2025Article
- Hepatocyte KCTD17-mediated SERPINA3 inhibition determines liver fibrosis in metabolic dysfunction-associated steatohepatitis.Experimental & molecular medicine · 2025Article
- RNA Modification in Metabolism.MedComm · 2025Review
- LncRNAs, RNA Therapeutics, and Emerging Technologies in Liver Pathobiology.Seminars in liver disease · 2025Review
- Identification of KCTD17 as a Ras stabilizer in hepatocellular carcinoma: Editorial on "KCTD17-mediated Ras stabilization promotes hepatocellular carcinoma progression".Clinical and molecular hepatology · 2025Article
- KCTD17-mediated Ras stabilization promotes hepatocellular carcinoma progression.Clinical and molecular hepatology · 2024Article
- Review
- The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating pyruvate kinase M2 ubiquitination.Journal of translational medicine · 2024Article
- Targeting E3 ubiquitin ligases and their adaptors as a therapeutic strategy for metabolic diseases.Experimental & molecular medicine · 2023Review
- The role of ChREBP in carbohydrate sensing and NAFLD development.Nature reviews. Endocrinology · 2023Review
- Unmasking the enigma of lipid metabolism in metabolic dysfunction-associated steatotic liver disease: from mechanism to the clinic.Frontiers in medicine · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsObesity predisposes to type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD), but underlying mechanisms are incompletely understood. Potassium channel tetramerization domain-containing protein 17 (Kctd17) levels are increased in livers from obese mice and humans. In this study, we investigated the mechanism of increased Kctd17 and whether it is causal to obesity-induced metabolic complications.
methodsWe transduced Rosa26-LSL-Cas9 knockin mice with AAV8-TBG-Cre (Control), AAV8-U6-Kctd17 sgRNA-TBG-Cre (L-Kctd17), AAV8-U6-Oga sgRNA-TBG-Cre (L-Oga), or AAV8-U6-Kctd17/Oga sgRNA-TBG-Cre (DKO). We fed mice a high-fat diet (HFD) and assessed for hepatic glucose and lipid homeostasis. We generated Kctd17, O-GlcNAcase (Oga), or Kctd17/Oga-knockout hepatoma cells by CRISPR-Cas9, and Kctd17-directed antisense oligonucleotide to test therapeutic potential in vivo. We analyzed transcriptomic data from patients with NAFLD.
resultsHepatocyte Kctd17 expression was increased in HFD-fed mice due to increased Srebp1c activity. HFD-fed L-Kctd17 or Kctd17 antisense oligonucleotide-treated mice show improved glucose tolerance and hepatic steatosis, whereas forced Kctd17 expression caused glucose intolerance and hepatic steatosis even in lean mice. Kctd17 induced Oga degradation, resulting in increasing carbohydrate response element-binding protein (Chrebp) protein, so concomitant Oga knockout negated metabolic benefits of hepatocyte Kctd17 deletion. In patients with NAFLD, KCTD17 messenger RNA was positively correlated with expression of Chrebp target and other lipogenic genes.
conclusionsSrebp1c-induced hepatocyte Kctd17 expression in obesity disrupted glucose and lipid metabolism by stabilizing Chrebp, and may represent a novel therapeutic target for obesity-induced T2D and NAFLD.
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.