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Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease.
- Source :
-
PloS one [PLoS One] 2014 Feb 04; Vol. 9 (2), pp. e88005. Date of Electronic Publication: 2014 Feb 04 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Introduction: 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.<br />Patients and 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.<br />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.<br />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.
- Subjects :
- Adolescent
Anti-Inflammatory Agents pharmacology
Child
Cytokines genetics
Cytokines metabolism
Fatty Liver genetics
Fatty Liver metabolism
Female
Hepatocytes drug effects
Hepatocytes metabolism
Hepatocytes pathology
Humans
Inflammation drug therapy
Inflammation genetics
Inflammation metabolism
Inflammation pathology
Liver metabolism
Macrophages drug effects
Macrophages metabolism
Macrophages pathology
Male
NF-kappa B genetics
NF-kappa B metabolism
Non-alcoholic Fatty Liver Disease
Receptors, G-Protein-Coupled genetics
Receptors, G-Protein-Coupled metabolism
Stem Cells drug effects
Stem Cells microbiology
Stem Cells pathology
Docosahexaenoic Acids pharmacology
Fatty Liver drug therapy
Fatty Liver pathology
Liver drug effects
Liver pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24505350
- Full Text :
- https://doi.org/10.1371/journal.pone.0088005