ArticleMolecular pharmacology2009
Bezafibrate at clinically relevant doses decreases serum/liver triglycerides via down-regulation of sterol regulatory element-binding protein-1c in mice: a novel peroxisome proliferator-activated receptor alpha-independent mechanism.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 70 citations in OpenAlex.
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- Is there a role of lipid-lowering therapies in the management of fatty liver disease?World journal of hepatology · 2022Review
- Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism.Metabolites · 2021Article
- Pemafibrate, a novel selective PPARα modulator, attenuates tamoxifen-induced fatty liver disease.Clinical journal of gastroenterology · 2021Article
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- MicroRNAs as a Novel Tool in the Diagnosis of Liver Lipid Dysregulation and Fatty Liver Disease.Molecules (Basel, Switzerland) · 2019Review
- Bezafibrate Prevents Glycine-Induced Increase of Antioxidant Enzyme Activities in Rat Striatum.Molecular neurobiology · 2019Article
- Elucidating the Beneficial Role of PPAR Agonists in Cardiac Diseases.International journal of molecular sciences · 2018Review
- The Effects of PPAR Stimulation on Cardiac Metabolic Pathways in Barth Syndrome Mice.Frontiers in pharmacology · 2018Article
- Targeting nuclear receptors for the treatment of fatty liver disease.Pharmacology & therapeutics · 2017Review
- The PPAR pan-agonist bezafibrate ameliorates cardiomyopathy in a mouse model of Barth syndrome.Orphanet journal of rare diseases · 2017Article
- Peroxisome Proliferator-Activated Receptors Associated with Nonalcoholic Fatty Liver Disease.PPAR research · 2017Review
- Age-dependent PPARα activation induces hepatic sulfatide accumulation in transgenic mice carrying the hepatitis C virus core gene.Glycoconjugate journal · 2016Article
- Effect of miR-34a in regulating steatosis by targeting PPARα expression in nonalcoholic fatty liver disease.Scientific reports · 2015Article
- Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans.Alcoholism, clinical and experimental research · 2015Article
- Turn up the power - pharmacological activation of mitochondrial biogenesis in mouse models.British journal of pharmacology · 2014Review
- Medium-chain triglyceride supplementation under a low-carbohydrate formula is a promising therapy for adult-onset type II citrullinemia.Molecular genetics and metabolism reports · 2014Article
- Novel PPAR pan agonist, ZBH ameliorates hyperlipidemia and insulin resistance in high fat diet induced hyperlipidemic hamster.PloS one · 2014Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The triglyceride-lowering effect of bezafibrate in humans has been attributed to peroxisome proliferator-activated receptor (PPAR) alpha activation based on results from rodent studies. However, the bezafibrate dosages used in conventional rodent experiments are typically higher than those in clinical use (> or =50 versus < or =10 mg/kg/day), and thus it remains unclear whether such data can be translated to humans. Furthermore, because bezafibrate is a pan-PPAR activator, the actual contribution of PPARalpha to its triglyceride-lowering properties remains undetermined. To address these issues, bezafibrate at clinically relevant doses (10 mg/kg/day; low) was administered to wild-type and Ppara-null mice, and its effects were compared with those from conventionally used doses (100 mg/kg/day; high). Pharmacokinetic analyses showed that maximum plasma concentration and area under the concentration-time curve in bezafibrate-treated mice were similar to those in humans at low doses, but not at high doses. Low-dose bezafibrate decreased serum/liver triglycerides in a PPARalpha-independent manner by attenuation of hepatic lipogenesis and triglyceride secretion. It is noteworthy that instead of PPAR activation, down-regulation of sterol regulatory element-binding protein (SREBP)-1c was observed in mice undergoing low-dose treatment. High-dose bezafibrate decreased serum/liver triglycerides by enhancement of hepatic fatty acid uptake and beta-oxidation via PPARalpha activation, as expected. In conclusion, clinically relevant doses of bezafibrate exert a triglyceride-lowering effect by suppression of the SREBP-1c-regulated pathway in mice and not by PPARalpha activation. Our results may provide novel information about the pharmacological mechanism of bezafibrate action and new insights into the treatment of disorders involving SREBP-1c.
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