NDLI: FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats.

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FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cipriani, Sabrina Mencarelli, Andrea Palladino, Giuseppe Fiorucci, Stefano
Description	Country affiliation: Italy Author Affiliation: Cipriani S ( Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia, Via E. dal Pozzo, Perugia, Italy.)
Abstract	The farnesoid X receptor (FXR) is a bile acid activated nuclear receptor. Zucker (fa/fa) rats, harboring a loss of function mutation of the leptin receptor, develop diabetes, insulin resistance, obesity, and liver steatosis. In this study, we investigated the effect of FXR activation by 6-ethyl-chenodeoxycholic acid, (6E-CDCA, 10 mg/kg) on insulin resistance and liver and muscle lipid metabolism in fa/fa rats and compared its activity with rosiglitazone (10 mg/kg) alone or in combination with 6E-CDCA (5 mg/kg each). In comparison to lean (fa/+), fa/fa rats on a normal diet developed insulin resistance and liver steatosis. FXR activation protected against body weight gain and liver and muscle fat deposition and reversed insulin resistance as assessed by insulin responsive substrate-1 phosphorylation on serine 312 in liver and muscles. Activation of FXR reduced liver expression of genes involved in fatty acid synthesis, lipogenesis, and gluconeogenesis. In the muscles, FXR treatment reduced free fatty acid synthesis. Rosiglitazone reduced blood insulin, glucose, triglyceride, free fatty acid, and cholesterol plasma levels but promoted body weight gain (20%) and liver fat deposition. FXR activation reduced high density lipoprotein plasma levels. In summary, FXR administration reversed insulin resistance and correct lipid metabolism abnormalities in an obesity animal model.
File Format	HTM / HTML
ISSN	00222275
e-ISSN	15397262
DOI	10.1194/jlr.M001602
Journal	The Journal of Lipid Research
Issue Number	4
Volume Number	51
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Biochemistry Chenodeoxycholic Acid Analogs & Derivatives Fatty Liver Prevention & Control Hypolipidemic Agents Therapeutic Use Insulin Resistance Lipid Metabolism Drug Effects Obesity Complications Receptors, Cytoplasmic And Nuclear Agonists Animals Administration & Dosage Disease Models, Animal Drug Therapy, Combination Blood Pathology Gene Expression Regulation Hypoglycemic Agents Insulin Receptor Substrate Proteins Metabolism Genetics Lipids Liver Muscle, Skeletal Phosphorylation Rna, Messenger Random Allocation Rats, Zucker Thiazolidinediones Time Factors Comparative Study
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Endocrinology

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FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats.

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FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa/fa) obese rats[S]

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