Laparoscopic Sleeve Gastrectomy Improves Nonalcoholic Fatty Liver Disease-Related Liver Damage in Adolescents by Reshaping Cellular Interactions and Hepatic Adipocytokine Production

Valerio Nobili, Guido Carpino, Francesco De Peppo, Romina Caccamo, Antonella Mosca, Ilaria Romito, Diletta Overi, Antonio Franchitto, Paolo Onori, Anna Alisi, Eugenio Gaudio

Research output: Contribution to journalArticle

Abstract

Objectives: To investigate whether the modulation of local cellular cross-talks and the modification of hepatic adipocytokine expression could mechanistically explain the improvement of liver histopathology after laparoscopic sleeve gastrectomy (LSG) in adolescents with nonalcoholic fatty liver disease (NAFLD). Study design: Twenty obese (body mass index of ≥35 kg/m2) adolescents who underwent LSG and with biopsy-proven NAFLD were included. At baseline (T0) and 1 year after treatment, patients underwent clinical evaluation, blood tests, and liver biopsy. Hepatic progenitor cells, hepatic stellate cells (HSCs), macrophages, and adipocytokines were evaluated by immunohistochemistry and immunofluorescence. Results: Liver biopsy samples after LSG demonstrated a significant improvement of NAFLD Activity Score and fibrosis. Immunohistochemistry indicated a significant reduction of hepatocyte cell cycle arrest, ductular reaction, activated HSC, and macrophage number after LSG compared with T0. The activation state of HSC was accompanied by modification in the expression of the autophagy marker LC3. Hepatocyte expression of adiponectin was significant higher after LSG than into T0. Moreover, LSG caused decreased resistin expression in Sox9+ hepatic progenitor cells compared with T0. The number of S100A9+ macrophages was also reduced by LSG correlating with resistin expression. Finally, serum levels of proinflammatory cytokines significantly correlated with macrophages and activated HSC numbers. Conclusions: The histologic improvement induced by LSG is associated with the reduced activation of local cellular compartments (hepatic progenitor cells, HSCs, and macrophages), thus, strengthening the role of cellular interactions and hepatic adipocytokine production in the pathogenesis of NAFLD.

Original languageEnglish
JournalJournal of Pediatrics
DOIs
Publication statusAccepted/In press - Jan 1 2017

Fingerprint

Adipokines
Gastrectomy
Hepatic Stellate Cells
Liver
Hepatocytes
Macrophages
Resistin
Stem Cells
Biopsy
Cell Count
Immunohistochemistry
Non-alcoholic Fatty Liver Disease
Adiponectin
Autophagy
Hematologic Tests
Cell Cycle Checkpoints
Fluorescent Antibody Technique
Body Mass Index
Fibrosis
Cytokines

Keywords

  • Adiponectin
  • Bariatric surgery
  • Ductular reaction
  • Hepatic progenitor cells
  • Resistin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Laparoscopic Sleeve Gastrectomy Improves Nonalcoholic Fatty Liver Disease-Related Liver Damage in Adolescents by Reshaping Cellular Interactions and Hepatic Adipocytokine Production. / Nobili, Valerio; Carpino, Guido; De Peppo, Francesco; Caccamo, Romina; Mosca, Antonella; Romito, Ilaria; Overi, Diletta; Franchitto, Antonio; Onori, Paolo; Alisi, Anna; Gaudio, Eugenio.

In: Journal of Pediatrics, 01.01.2017.

Research output: Contribution to journalArticle

@article{d8ca3d3194264c7bb0a2edf79e786bbd,
title = "Laparoscopic Sleeve Gastrectomy Improves Nonalcoholic Fatty Liver Disease-Related Liver Damage in Adolescents by Reshaping Cellular Interactions and Hepatic Adipocytokine Production",
abstract = "Objectives: To investigate whether the modulation of local cellular cross-talks and the modification of hepatic adipocytokine expression could mechanistically explain the improvement of liver histopathology after laparoscopic sleeve gastrectomy (LSG) in adolescents with nonalcoholic fatty liver disease (NAFLD). Study design: Twenty obese (body mass index of ≥35 kg/m2) adolescents who underwent LSG and with biopsy-proven NAFLD were included. At baseline (T0) and 1 year after treatment, patients underwent clinical evaluation, blood tests, and liver biopsy. Hepatic progenitor cells, hepatic stellate cells (HSCs), macrophages, and adipocytokines were evaluated by immunohistochemistry and immunofluorescence. Results: Liver biopsy samples after LSG demonstrated a significant improvement of NAFLD Activity Score and fibrosis. Immunohistochemistry indicated a significant reduction of hepatocyte cell cycle arrest, ductular reaction, activated HSC, and macrophage number after LSG compared with T0. The activation state of HSC was accompanied by modification in the expression of the autophagy marker LC3. Hepatocyte expression of adiponectin was significant higher after LSG than into T0. Moreover, LSG caused decreased resistin expression in Sox9+ hepatic progenitor cells compared with T0. The number of S100A9+ macrophages was also reduced by LSG correlating with resistin expression. Finally, serum levels of proinflammatory cytokines significantly correlated with macrophages and activated HSC numbers. Conclusions: The histologic improvement induced by LSG is associated with the reduced activation of local cellular compartments (hepatic progenitor cells, HSCs, and macrophages), thus, strengthening the role of cellular interactions and hepatic adipocytokine production in the pathogenesis of NAFLD.",
keywords = "Adiponectin, Bariatric surgery, Ductular reaction, Hepatic progenitor cells, Resistin",
author = "Valerio Nobili and Guido Carpino and {De Peppo}, Francesco and Romina Caccamo and Antonella Mosca and Ilaria Romito and Diletta Overi and Antonio Franchitto and Paolo Onori and Anna Alisi and Eugenio Gaudio",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.jpeds.2017.10.036",
language = "English",
journal = "Journal of Pediatrics",
issn = "0022-3476",
publisher = "Mosby Inc.",

}

TY - JOUR

T1 - Laparoscopic Sleeve Gastrectomy Improves Nonalcoholic Fatty Liver Disease-Related Liver Damage in Adolescents by Reshaping Cellular Interactions and Hepatic Adipocytokine Production

AU - Nobili, Valerio

AU - Carpino, Guido

AU - De Peppo, Francesco

AU - Caccamo, Romina

AU - Mosca, Antonella

AU - Romito, Ilaria

AU - Overi, Diletta

AU - Franchitto, Antonio

AU - Onori, Paolo

AU - Alisi, Anna

AU - Gaudio, Eugenio

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Objectives: To investigate whether the modulation of local cellular cross-talks and the modification of hepatic adipocytokine expression could mechanistically explain the improvement of liver histopathology after laparoscopic sleeve gastrectomy (LSG) in adolescents with nonalcoholic fatty liver disease (NAFLD). Study design: Twenty obese (body mass index of ≥35 kg/m2) adolescents who underwent LSG and with biopsy-proven NAFLD were included. At baseline (T0) and 1 year after treatment, patients underwent clinical evaluation, blood tests, and liver biopsy. Hepatic progenitor cells, hepatic stellate cells (HSCs), macrophages, and adipocytokines were evaluated by immunohistochemistry and immunofluorescence. Results: Liver biopsy samples after LSG demonstrated a significant improvement of NAFLD Activity Score and fibrosis. Immunohistochemistry indicated a significant reduction of hepatocyte cell cycle arrest, ductular reaction, activated HSC, and macrophage number after LSG compared with T0. The activation state of HSC was accompanied by modification in the expression of the autophagy marker LC3. Hepatocyte expression of adiponectin was significant higher after LSG than into T0. Moreover, LSG caused decreased resistin expression in Sox9+ hepatic progenitor cells compared with T0. The number of S100A9+ macrophages was also reduced by LSG correlating with resistin expression. Finally, serum levels of proinflammatory cytokines significantly correlated with macrophages and activated HSC numbers. Conclusions: The histologic improvement induced by LSG is associated with the reduced activation of local cellular compartments (hepatic progenitor cells, HSCs, and macrophages), thus, strengthening the role of cellular interactions and hepatic adipocytokine production in the pathogenesis of NAFLD.

AB - Objectives: To investigate whether the modulation of local cellular cross-talks and the modification of hepatic adipocytokine expression could mechanistically explain the improvement of liver histopathology after laparoscopic sleeve gastrectomy (LSG) in adolescents with nonalcoholic fatty liver disease (NAFLD). Study design: Twenty obese (body mass index of ≥35 kg/m2) adolescents who underwent LSG and with biopsy-proven NAFLD were included. At baseline (T0) and 1 year after treatment, patients underwent clinical evaluation, blood tests, and liver biopsy. Hepatic progenitor cells, hepatic stellate cells (HSCs), macrophages, and adipocytokines were evaluated by immunohistochemistry and immunofluorescence. Results: Liver biopsy samples after LSG demonstrated a significant improvement of NAFLD Activity Score and fibrosis. Immunohistochemistry indicated a significant reduction of hepatocyte cell cycle arrest, ductular reaction, activated HSC, and macrophage number after LSG compared with T0. The activation state of HSC was accompanied by modification in the expression of the autophagy marker LC3. Hepatocyte expression of adiponectin was significant higher after LSG than into T0. Moreover, LSG caused decreased resistin expression in Sox9+ hepatic progenitor cells compared with T0. The number of S100A9+ macrophages was also reduced by LSG correlating with resistin expression. Finally, serum levels of proinflammatory cytokines significantly correlated with macrophages and activated HSC numbers. Conclusions: The histologic improvement induced by LSG is associated with the reduced activation of local cellular compartments (hepatic progenitor cells, HSCs, and macrophages), thus, strengthening the role of cellular interactions and hepatic adipocytokine production in the pathogenesis of NAFLD.

KW - Adiponectin

KW - Bariatric surgery

KW - Ductular reaction

KW - Hepatic progenitor cells

KW - Resistin

UR - http://www.scopus.com/inward/record.url?scp=85035804637&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85035804637&partnerID=8YFLogxK

U2 - 10.1016/j.jpeds.2017.10.036

DO - 10.1016/j.jpeds.2017.10.036

M3 - Article

AN - SCOPUS:85035804637

JO - Journal of Pediatrics

JF - Journal of Pediatrics

SN - 0022-3476

ER -