Published online Jan 28, 2018. doi: 10.3748/wjg.v24.i4.461
Peer-review started: September 12, 2017
First decision: October 18, 2017
Revised: November 22, 2017
Accepted: November 28, 2017
Article in press: November 28, 2017
Published online: January 28, 2018
Processing time: 136 Days and 11.8 Hours
To study the effect of 18-hydroxy-eicosapentaenoic acid (18-HEPE) and 17-hydroxy-docosahexaenoic acid (17-HDHA) in a murine model of obesity/nonalcoholic fatty liver disease.
C57BL/6 mice were fed with standard chow diet (CD) or high-fat, fructose-enriched diet (HFD) for 16 wk. Then, three groups were treated for 14 d with either, diet switch (HFD for CD), 18-HEPE, or 17-HDHA. Weight and fasting glucose were recorded on a weekly basis. Insulin tolerance test was performed at the end of treatment. Histological analysis (HE and Masson’s trichrome stain) and determination of serum insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide, adiponectin and resistin were carried out as well as liver proteins by western blot.
Mice treated with hydroxy-fatty acids 18-HEPE and 17-HDHA displayed no weight loss or improved insulin sensitivity. However, these mice groups showed a significant amelioration on serum GLP-1, adiponectin and resistin levels. Also, a significant reduction on inflammatory infiltrate was observed at both portal and lobular zones. Furthermore, up-regulation of PPARα/γ protein levels was observed in liver tissue and it was associated with decreased levels of NF-κB also determined by western blot analysis. On the other hand, diet switch regimen resulted in a marked improvement in most parameters including: weight loss, increased insulin sensitivity, decreased steatosis, restored levels of insulin, glucagon, leptin, adiponectin and resistin. However, no significant changes were observed regarding inflammatory infiltrate in this last group.
18-HEPE and 17-HDHA differentially exert hepatoprotective effects through up-regulation of nuclear receptors PPARα/γ and amelioration of serum adipokines profile.
Core tip: Our study aimed to prove the efficacy of hydroxy-fatty acids 18-hydroxy-eicosapentaenoic acid and 17-hydroxy-docosahexaenoic acid (17-HDHA) in an obesity/nonalcoholic fatty liver disease (NAFLD) model in mice. We determined the effect of these molecules on histological morphology as well as in protein levels of key nuclear receptors and serum hormones, incretins and adipokines as these parameters are altered in NAFLD. We reported an effect by these hydroxy-fatty acids on the most relevant target proteins involved in this pathological process (PPARα/γ). Also, we demonstrated that diet switch regimen is a selective treatment control as most NAFLD markers and histological alterations were ameliorated by this intervention.