title: 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.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy, University of Naples Federico II, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Mattace Raso
authors.forename: Raffaele
authors.initials: R
authors.lastname: Simeoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Russo
authors.forename: Anna
authors.initials: A
authors.lastname: Iacono
authors.forename: Anna
authors.initials: A
authors.lastname: Santoro
authors.forename: Orlando
authors.initials: O
authors.lastname: Paciello
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Ferrante
authors.forename: Roberto Berni
authors.initials: RB
authors.lastname: Canani
authors.forename: Antonio
authors.initials: A
authors.lastname: Calignano
authors.forename: Rosaria
authors.initials: R
authors.lastname: Meli
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D020148:Butyric Acid / Q000008:administration & dosage / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D005234:Fatty Liver / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D005947:Glucose / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000577:Amides; D016328:NF-kappa B; D051193:Toll-Like Receptors; D020148:Butyric Acid; C006866:butyramide; D005947:Glucose