ArticleGut2016
Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD.
Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 403 papers, 3 of them syntheses that pooled it.
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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
403 citing papers in PubMed, 3 syntheses or guidelines pooled it, 707 citations in OpenAlex.
- The biomedical application of inorganic metal nanoparticles in aging and aging-associated diseases.Journal of advanced research · 2025Pooled it
- A Systematic Review of Statins for the Treatment of Nonalcoholic Steatohepatitis: Safety, Efficacy, and Mechanism of Action.Molecules (Basel, Switzerland) · 2024Pooled it
- The Role of Cannabidiol in Liver Disease: A Systemic Review.International journal of molecular sciences · 2024Pooled it
- Expression of PGC-1α, PPAR-α and UCP1 genes, metabolic and anthropometric factors in response to sodium butyrate supplementation in patients with obesity: a triple-blind, randomized placebo-controlled clinical trial.European journal of clinical nutrition · 2025Trial
- Dietary interaction of soybean oil and high starch impairs growth performance via metabolic-inflammatory dysregulation in Siberian sturgeon (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Furan fatty acids reprogram hepatic lipid metabolism via acyl-CoA conjugates in obesity.Science advances · 2026Article
- Adrenal hormones in the maintenance of glucose homeostasis during prolonged fasting in male glucagon-deficient mice.Journal of diabetes investigation · 2026Article
- Lipoprotein biology during induced oogenesis in the short-finned eel, Anguilla australis-hepatic target gene expression and accumulation of nutrient sources into developing oocytes.Fish physiology and biochemistry · 2026Article
- Interleukin13 Ameliorates Hepatocellular Steatosis via IL13Rα1/JNK/FOSL2 Signaling Pathway.Cellular and molecular gastroenterology and hepatology · 2026Article
- MicroRNA-34a Promotes Hepatic Lipid Accumulation Through RXRα Suppression and Is Reversed by 9-International journal of molecular sciences · 2026Article
- PPARMolecular nutrition & food research · 2026Article
- DNMT1 facilitates the progression of metabolic dysfunction-associated steatotic liver disease by impeding transcription mediated by HNF4α and PPARα.Clinical and molecular hepatology · 2026Article
- Transcriptomic Insights into Micro- and Nanoplastic Toxicity in Zebrafish: A Narrative Review.Toxics · 2026Review
- Exploring Toxicological Mechanisms of Typical PFAS-Induced NAFLD through Integrated Computational Toxicology and AOP Frameworks.Environment & health (Washington, D.C.) · 2026Article
- Loss of peroxisomal membrane proteins PEX13 and PEX14 disrupts fatty acid oxidation and drives lipid imbalance.Bioscience reports · 2026Article
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- Soft fibrin matrix instructs macrophage M2 polarization via FABP4-mediated enhancement of fatty acid β-oxidation to alleviate MASH.Cellular and molecular life sciences : CMLS · 2026Article
- Hepatic FGF21 is not required for fasting metabolism but guides protein appetite post energy depletion.EMBO reports · 2026Article
- Undernutrition-related diabetes in mice is linked to early undernutrition.American journal of physiology. Endocrinology and metabolism · 2026Article
343 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePeroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARα on non-alcoholic fatty liver disease (NAFLD).
designWe constructed a novel hepatocyte-specific PPARα knockout (Pparα(hep-/-)) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we investigated which physiological challenges impact on PPARα. Moreover, we measured the contribution of hepatocytic PPARα activity to whole-body metabolism and fibroblast growth factor 21 production during fasting. Finally, we determined the influence of hepatocyte-specific PPARα deficiency in different models of steatosis and during ageing.
resultsHepatocyte PPARα deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis. Fasting mice showed acute PPARα-dependent hepatocyte activity during early night, with correspondingly increased circulating free fatty acids, which could be further stimulated by adipocyte lipolysis. Fasting led to mild hypoglycaemia and hypothermia in Pparα(hep-/-) mice when compared with Pparα(-/-) mice implying a role of PPARα activity in non-hepatic tissues. In agreement with this observation, Pparα(-/-) mice became overweight during ageing while Pparα(hep-/-) remained lean. However, like Pparα(-/-) mice, Pparα(hep-/-) fed a standard diet developed hepatic steatosis in ageing.
conclusionsAltogether, these findings underscore the potential of hepatocyte PPARα as a drug target for 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.