ArticleGut2021
Hepatic Krüppel-like factor 16 (KLF16) targets PPARα to improve steatohepatitis and insulin resistance.
Article in Gut, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- A bibliometric analysis of the Mediterranean diet in metabolic syndrome (2015-2025).Frontiers in nutrition · 2026Pooled it
- Cardiovascular-kidney-metabolic syndrome as a mitochondrial systems disorder.Nature reviews. Nephrology · 2026Review
- KLF16 promotes immune escape in hepatocellular carcinoma cells by upregulating PD-L1 expression via PRKDC.Translational oncology · 2026Article
- Regulatory roles and translational potential of the Kruppel-like factor family in liver disease.iLIVER · 2026Review
- Ginseng-containing Shentao Ruangan (STR) formula alleviates hepatic fibrosis via hepatocellular Nrf2-ROS-TGF-β axis regulating hepatocyte-HSC crosstalk: Integrating single-cell RNA sequencing and multi-tiered validation.Journal of ginseng research · 2026Article
- Electroacupuncture activates the TET1/PPARα pathway to protect mitochondrial function in MASLD.Journal of inflammation (London, England) · 2026Article
- Role of oxidative stress in sepsis: Mechanisms, pathways, and therapeutic strategies.Journal of pharmaceutical analysis · 2026Review
- Salvianolic Acid B Alleviates MAFLD by Targeting PPAR-α: Mechanistic Insights From Network Pharmacology and Lipidomics.Food science & nutrition · 2026Article
- Medium-chain triglycerides improve cognition and systemic metabolism in mouse models of Alzheimer's disease.Brain : a journal of neurology · 2026Article
- Electroacupuncture in the treatment of non-alcoholic fatty liver disease: mechanistic insights and therapeutic potential.Frontiers in medicine · 2026Review
- Baihe Gujin decoction ameliorates sepsis-induced acute lung injury through Nrf2/GPX4-mediated antioxidant defense and PPARα-driven metabolic reprogramming: a multi-omics investigation.Frontiers in immunology · 2026Article
- UBC9 silencing-mediated PPARα deSUMOylation induces inhibition of cell proliferation by ferroptosis in acute myeloid leukemia.Archives of medical science : AMS · 2026Article
- L-Theanine ameliorates high-protein diet-associated hepatic glucose and lipid metabolic alterations by promoting fatty acid β-oxidation and suppressing lipid synthesis and gluconeogenesis in rats.Current research in food science · 2026Article
- Macrophage Nrf1/NFE2L1-Foxo1 axis controls liver fibrosis by modulation of mitochondrial reprogramming.Theranostics · 2026Article
- Progress and Practice of Insulin Resistance in Pregnancy: From Pathogenesis to Management.International journal of medical sciences · 2026Review
- Review
- GPX8 is transcriptionally regulated by KLF16 and promotes osteosarcoma progression.Journal of translational medicine · 2025Article
- The role of the transcription factor KLF16 in metabolic dysfunction associated fatty liver disease: regulatory linkages between lipid deposition and the expression of ATF4.Annals of medicine · 2025Article
- Licochalcone A ameliorates lipid accumulation in metabolic dysfunction-associated steatotic liver disease via upregulating PPARα/CPT1α.Histology and histopathology · 2025Article
- From Nuclear Receptor Regulation to Spleen Activating and Accumulation Resolving Therapy: A Review of Traditional Chinese Medicine Against Diabetes and Inflammation.International journal of molecular sciences · 2025Review
16 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
17 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveImpaired hepatic fatty acids oxidation results in lipid accumulation and redox imbalance, promoting the development of fatty liver diseases and insulin resistance. However, the underlying pathogenic mechanism is poorly understood. Krüppel-like factor 16 (KLF16) is a transcription factor that abounds in liver. We explored whether and by what mechanisms KLF16 affects hepatic lipid catabolism to improve hepatosteatosis and insulin resistance.
designKLF16 expression was determined in patients with non-alcoholic fatty liver disease (NAFLD) and mice models. The role of KLF16 in the regulation of lipid metabolism was investigated using hepatocyte-specific KLF16-deficient mice fed a high-fat diet (HFD) or using an adenovirus/adeno-associated virus to alter KLF16 expression in mouse primary hepatocytes (MPHs) and in vivo livers. RNA-seq, luciferase reporter gene assay and ChIP analysis served to explore the molecular mechanisms involved.
resultsKLF16 expression was decreased in patients with NAFLD, mice models and oleic acid and palmitic acid (OA and PA) cochallenged hepatocytes. Hepatic KLF16 knockout impaired fatty acid oxidation, aggravated mitochondrial stress, ROS burden, advancing hepatic steatosis and insulin resistance. Conversely, KLF16 overexpression reduced lipid deposition and improved insulin resistance via directly binding the promoter of peroxisome proliferator-activated receptor α (PPARα) to accelerate fatty acids oxidation and attenuate mitochondrial stress, oxidative stress in
conclusionsThese findings prove that a direct KLF16-PPARα pathway closely links hepatic lipid homeostasis and redox balance, whose dysfunction promotes insulin resistance and hepatic steatosis.
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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.