title: Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool.
  
  
  METHODS
  20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters.
  
  
  RESULTS
  GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines.
  
  
  CONCLUSIONS
  DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival.
authors: Unit of Liver Research, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Valerio
authors: V
authors: Nobili
authors: Department of Movement, Human and Health Sciences, University of Rome "Foro Italico", Rome, Italy.
authors: Guido
authors: G
authors: Carpino
authors: Unit of Liver Research, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Anna
authors: A
authors: Alisi
authors: Unit of Pathology, Bambino Gesù Children's Hospital, Rome, Italy.
authors: Rita
authors: R
authors: De Vito
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy ; Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy.
authors: Antonio
authors: A
authors: Franchitto
authors: Department of Medicine, Scott & White and Texas A&M Health Science Center College of Medicine, Temple, Texas, United States of America.
authors: Gianfranco
authors: G
authors: Alpini
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
authors: Paolo
authors: P
authors: Onori
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, Rome, Italy.
authors: Eugenio
authors: E
authors: Gaudio
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000382:microbiology / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; C519853:FFAR4 protein, human; D016328:NF-kappa B; D043562:Receptors, G-Protein-Coupled; D004281:Docosahexaenoic Acids