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

doi:10.1016/j.jpeds.2017.10.036

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

J Pediatr. 2018 Mar:194:100-108.e3. doi: 10.1016/j.jpeds.2017.10.036. Epub 2017 Dec 1.

Authors

Affiliations

¹ Hepatometabolic Unit, Bambino Gesù Children's Hospital, Rome, Italy; Department of Pediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Italy. Electronic address: nobili66@yahoo.it.
² Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
³ Pediatric Surgery Unit, Bambino Gesù Children's Hospital, Palidoro, Roma, Italy.
⁴ Hepatometabolic Unit, Bambino Gesù Children's Hospital, Rome, Italy.
⁵ Liver Research Unit, Bambino Gesù Children's Hospital, Rome, Italy.
⁶ Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.

PMID: 29198531
DOI: 10.1016/j.jpeds.2017.10.036

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipokines / physiology*
Adolescent
Body Mass Index
Cohort Studies
Female
Gastrectomy*
Hepatocytes / physiology*
Humans
Laparoscopy*
Liver Cirrhosis / etiology
Liver Cirrhosis / pathology
Liver Cirrhosis / therapy
Male
Non-alcoholic Fatty Liver Disease / etiology
Non-alcoholic Fatty Liver Disease / pathology*
Non-alcoholic Fatty Liver Disease / therapy
Pediatric Obesity / complications
Pediatric Obesity / pathology
Pediatric Obesity / surgery*

Substances

Adipokines