title: Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis, insulin signaling and toll-like receptor expression in rats fed a high-fat diet.
abstract: Insulin resistance (IR) has been identified as crucial pathophysiological factor in the development and progression of non-alcoholic fatty liver disease (NAFLD). Although mounting evidence suggests that perturbation of gut microflora exacerbates the severity of chronic liver diseases, therapeutic approaches using synbiotic has remained overlooked. Here, we show that a synbiotic composed by Lactobacillus paracasei B21060 plus arabinogalactan and fructo-oligosaccharides lessens NAFLD progression in a rat model of high fat feeding. IR and steatosis were induced by administration of high fat diet (HFD) for 6 weeks. Steatosis and hepatic inflammation, Toll-like receptor (TLR) pattern, glucose tolerance, insulin signaling and gut permeability were studied. Liver inflammatory markers were down-regulated in rats receiving the synbiotic, along with an increased expression of nuclear peroxisome proliferator-activated receptors and expression of downstream target genes. The synbiotic improved many aspects of IR, such as fasting response, hormonal homeostasis and glycemic control. Indeed it prevented the impairment of hepatic insulin signaling, reducing the phosphorylation of insulin receptor substrate-1 in Ser 307 and down-regulating suppressor of cytokine signaling 3. Gene expression analysis revealed that in the liver the synbiotic reduced cytokines synthesis and restored the HFD-dysregulated TLR 2, 4 and 9 mRNAs toward a physiological level of expression. The synbiotic preserved gut barrier integrity and reduced the relative amount of Gram-negative Enterobacteriales and Escherichia coli in colonic mucosa. Overall, our data indicate that the L. paracasei B21060 based synbiotic is effective in reducing the severity of liver injury and IR associated with high fat intake, suggesting its possible therapeutic/preventive clinical utilization.
authors: Department of Pharmacy, University of Naples "Federico II", 80131 Naples, Italy.
authors: Giuseppina Mattace
authors: GM
authors: Raso
authors: Raffaele
authors: R
authors: Simeoli
authors: Anna
authors: A
authors: Iacono
authors: Anna
authors: A
authors: Santoro
authors: Paola
authors: P
authors: Amero
authors: Orlando
authors: O
authors: Paciello
authors: Roberto
authors: R
authors: Russo
authors: Giuseppe
authors: G
authors: D'Agostino
authors: Margherita
authors: M
authors: Di Costanzo
authors: Roberto Berni
authors: RB
authors: Canani
authors: Antonio
authors: A
authors: Calignano
authors: Rosaria
authors: R
authors: Meli
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D015536:Down-Regulation; D004755:Enterobacteriaceae / Q000187:drug effects; D005234:Fatty Liver / Q000628:therapy*; D005685:Galactans / Q000494:pharmacology; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology; D007778:Lactobacillus; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009844:Oligosaccharides / Q000494:pharmacology; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D058616:Synbiotics; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D005685:Galactans; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D009844:Oligosaccharides; D047495:PPAR gamma; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C495343:Tlr2 protein, rat; C495347:Tlr4 protein, rat; C489640:Tlr9 protein, rat; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C116580:fructooligosaccharide; C005653:arabinogalactan
keywords: Glucose tolerance; Gut permeability; Inflammation; Insulin resistance; Non-alcoholic fatty liver disease; Toll-like receptor