ArticlePloS one2013
Concurrent activation of liver X receptor and peroxisome proliferator-activated receptor alpha exacerbates hepatic steatosis in high fat diet-induced obese mice.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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.
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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
38 citing papers in PubMed, 67 citations in OpenAlex.
- Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: a randomized controlled trial.Hepatology (Baltimore, Md.) · 2014Trial
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- Plant miR8126-3p and miR8126-5p Decrease Lipid Accumulation through Modulation of Metabolic Genes in a Human Hepatocyte Model That Mimics Steatosis.International journal of molecular sciences · 2024Article
- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- Liver Protective Effect of Fenofibrate in NASH/NAFLD Animal Models.PPAR research · 2022Review
- Review
- Frontline Science: Activation of metabolic nuclear receptors restores periodontal tissue homeostasis in mice with leukocyte adhesion deficiency-1.Journal of leukocyte biology · 2020Article
- A Small Molecule, UAB126, Reverses Diet-Induced Obesity and its Associated Metabolic Disorders.Diabetes · 2020Article
- Akkermansia muciniphila Prevents Fatty Liver Disease, Decreases Serum Triglycerides, and Maintains Gut Homeostasis.Applied and environmental microbiology · 2020Article
- Controlling Obesity and Metabolic Diseases by Hydrodynamic Delivery of a Fusion Gene of Exendin-4 and α1 Antitrypsin.Scientific reports · 2019Article
- Induction of Stearoyl-CoA 9-Desaturase 1 Protects Human Mesenchymal Stromal Cells Against Palmitic Acid-Induced Lipotoxicity and Inflammation.Frontiers in endocrinology · 2019Article
- Inhibition of Hepatotoxicity by a LXR Inverse Agonist in a Model of Alcoholic Liver Disease.ACS pharmacology & translational science · 2018Article
- Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors.International journal of molecular sciences · 2018Review
- The Role of PPAR and Its Cross-Talk with CAR and LXR in Obesity and Atherosclerosis.International journal of molecular sciences · 2018Review
- Organophosphate Flame-Retardants Alter Adult Mouse Homeostasis and Gene Expression in a Sex-Dependent Manner Potentially Through Interactions With ERα.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- G0S2: A small giant controller of lipolysis and adipose-liver fatty acid flux.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2017Review
- Morin, a novel liver X receptor α/β dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases.British journal of pharmacology · 2017Article
- CRISPR/Cas9-based Pten knock-out and Sleeping Beauty Transposon-mediated Nras knock-in induces hepatocellular carcinoma and hepatic lipid accumulation in mice.Cancer biology & therapy · 2017Article
- Fenofibrate, but not ezetimibe, prevents fatty liver disease in mice lacking phosphatidylethanolamineJournal of lipid research · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Liver X receptor (LXR) activation improves glucose homeostasis in obesity. This improvement, however, is associated with several side effects including hyperlipidemia and hepatic steatosis. Activation of peroxisome proliferator-activated receptor alpha (PPARα), on the other hand, increases fatty acid oxidation, leading to a reduction of hyperlipidemia. The objective of this study was to investigate whether concurrent activation of LXR/PPARα can produce synergistic benefits in treating obesity-associated metabolic disorders. Treatment of high fat diet-induced obese mice with T0901317, an LXR activator, or fenofibrate, the PPARα agonist, or in combination alleviated insulin resistance and improved glucose tolerance. The combined treatment dramatically exacerbated hepatic steatosis. Gene expression analysis in the liver showed that combined treatment increased the expression of genes involved in lipogenesis and fatty acid transport, including srebp-1c, chrebp, acc1, fas, scd1 and cd36. Histochemistry and ex vivo glycerol releasing assay showed that combined treatment accelerated lipid mobilization in adipose tissue. Combined treatment also increased the transcription of glut4, hsl, atgl and adiponectin, and decreased that of plin1, cd11c, ifnγ and leptin. Combined treatment markedly elevated the transcription of fgf21 in liver but not in adipose tissue. These results suggest that concurrent activation of LXR and PPARα as a strategy to control glucose and lipid metabolism in obesity is beneficial but could lead to elevation of lipid accumulation in the liver.
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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.