Altered gut-liver axis and hepatic adiponectin expression in OSAS: Novel mediators of liver injury in paediatric non-alcoholic fatty liver

Valerio Nobili, Anna Alisi, Renato Cutrera, Guido Carpino, Cristiano De Stefanis, Valentina D'Oria, Rita De Vito, Salvatore Cucchiara, Eugenio Gaudio, Giovanni Musso

Research output: Contribution to journalArticle

Abstract

Background Mechanism(s) connecting obstructive sleep apnoea syndrome (OSAS) to liver injury in paediatric non-alcoholic fatty liver disease (NAFLD) are unknown. We hypothesised alterations in gut-liver axis and in the pool and phenotype of hepatic progenitor cells (HPCs) may be involved in OSAS-associated liver injury in NAFLD. Methods Eighty biopsy-proven NAFLD children (age, mean±SD, 11.4±2.0 years, 56% males, body mass index z-score 1.95±0.57) underwent a clinical- biochemical assessment, with measurement of insulin sensitivity, plasma cytokines, lipopolysaccharide (LPS), an intestinal permeability test and a standard polysomnography. Hepatic toll-like receptor (TLR)-4 expression by liver-resident cells and overall number and expression of resistin and adiponectin by HPCs were assessed by immunofluorescence and immunohistochemistry. OSAS was defined by an apnoea/ hypopnoea index ≥1. Results OSAS was characterised by an increased intestinal permeability and endotoxemia, coupled with TLR-4 upregulation in hepatocytes, Kupffer and hepatic stellate cells (HSCs) and by an expansion of an adiponectin-deficient HPC pool, key features of steatohepatitis and fibrosis. The duration of haemoglobin desaturation (SaO2

Original languageEnglish
Pages (from-to)769-781
Number of pages13
JournalThorax
Volume70
Issue number8
DOIs
Publication statusPublished - Aug 1 2015

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

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