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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Adiponectin
Obstructive Sleep Apnea
Fatty Liver
Pediatrics
Hepatocytes
Liver
Wounds and Injuries
Toll-Like Receptor 4
Stem Cells
Permeability
Resistin
Hepatic Stellate Cells
Endotoxemia
Polysomnography
Apnea
Fluorescent Antibody Technique
Lipopolysaccharides
Insulin Resistance
Hemoglobins
Body Mass Index

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

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Altered gut-liver axis and hepatic adiponectin expression in OSAS : Novel mediators of liver injury in paediatric non-alcoholic fatty liver. / Nobili, Valerio; Alisi, Anna; Cutrera, Renato; Carpino, Guido; De Stefanis, Cristiano; D'Oria, Valentina; De Vito, Rita; Cucchiara, Salvatore; Gaudio, Eugenio; Musso, Giovanni.

In: Thorax, Vol. 70, No. 8, 01.08.2015, p. 769-781.

Research output: Contribution to journalArticle

Nobili, Valerio ; Alisi, Anna ; Cutrera, Renato ; Carpino, Guido ; De Stefanis, Cristiano ; D'Oria, Valentina ; De Vito, Rita ; Cucchiara, Salvatore ; Gaudio, Eugenio ; Musso, Giovanni. / Altered gut-liver axis and hepatic adiponectin expression in OSAS : Novel mediators of liver injury in paediatric non-alcoholic fatty liver. In: Thorax. 2015 ; Vol. 70, No. 8. pp. 769-781.
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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",
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AU - Cutrera, Renato

AU - Carpino, Guido

AU - De Stefanis, Cristiano

AU - D'Oria, Valentina

AU - De Vito, Rita

AU - Cucchiara, Salvatore

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AU - Musso, Giovanni

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N2 - 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

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