Effects of sodium butyrate and its synthetic amide derivative on liver inflammation and glucose tolerance in an animal model of steatosis induced by high fat diet

• Published in: PloS one Vol. 8; no. 7; p. e68626
• Main Authors: Mattace Raso, Giuseppina, Simeoli, Raffaele, Russo, Roberto, Iacono, Anna, Santoro, Anna, Paciello, Orlando, Ferrante, Maria Carmela, Canani, Roberto Berni, Calignano, Antonio, Meli, Rosaria
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.07.2013; Public Library of Science (PLoS)
• Subjects: Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Amides - administration & dosage; Amides - pharmacology; Animal tissues; Animals; Butyric Acid - administration & dosage; Butyric Acid - pharmacology; Diabetes; Diet; Diet therapy; Diet, High-Fat - adverse effects; Disease Models, Animal; Disease resistance; Enzyme Activation - drug effects; Esters; Fatty acids; Fatty liver; Fatty Liver - drug therapy; Fatty Liver - etiology; Fatty Liver - metabolism; Fatty Liver - pathology; Gene expression; Glucose; Glucose - metabolism; Glucose tolerance; Growth factors; High fat diet; Homeostasis; Inflammation; Inflammation - metabolism; Inflammation - pathology; Insulin; Insulin Resistance; Kinases; Lipids; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver diseases; Male; Metabolic disorders; Neural networks; NF-kappa B - metabolism; NF-κB protein; Non-alcoholic Fatty Liver Disease; Palatability; Pathogenesis; Pharmacy; Proteins; Rats; Receptors; Rodents; Sodium; Sodium butyrate; Steatosis; Toll-like receptors; Toll-Like Receptors - metabolism; Transaminases; Tumor necrosis factor-α; Veins & arteries; Veterinary medicine; Weaning
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0068626

Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Insulin resistance (IR) appears to be critical in its pathogenesis. We evaluated the effects of sodium butyrate (butyrate) and its synthetic derivative N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) in a rat model of insulin resistance and steatosis induced by high-fat diet (HFD). After weaning, young male Sprague-Dawley rats were divided into 4 groups receiving different diets for 6 weeks: 1. control group (standard diet); 2. HFD; 3. HFD plus butyrate (20 mg/kg/die) and 4. HFD plus FBA (42.5 mg/Kg/die, the equimolecular dose of butyrate). Liver tissues of the rats were analyzed by Western blot and real-time PCR. Insulin resistance, liver inflammation and Toll-like pattern modifications were determined. Evaluation of these two preparations of butyrate showed a reduction of liver steatosis and inflammation in HFD fed animals. The compounds showed a similar potency in the normalisation of several variables, such as transaminases, homeostasis model assessment for insulin resistance index, and glucose tolerance. Both treatments significantly reduced hepatic TNF-α expression and restored GLUTs and PPARs, either in liver or adipose tissue. Finally, FBA showed a higher potency in reducing pro-inflammatory parameters in the liver, via suppression of Toll-like receptors and NF-κB activation. Our results demonstrated a protective effect of butyrate in limiting molecular events underlying the onset of IR and NAFLD, suggesting a potential clinical relevance for this substance. In particular, its derivative, FBA, could represent an alternative therapeutic option to sodium butyrate, sharing a comparable efficacy, but a better palatability and compliance.