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
Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver condition over the last decades. Notably, NAFLD shows a high growth rate worldwide and it is thought to derive mainly from modern lifestyle habits featuring low physical activity and chronic exposure to high-fat, high-fructose diet. Those mentioned factors have dramatically increased the prevalence of obesity and metabolic syndrome along with its comorbidities: dyslipidemia, insulin resistance, and hypertension.
Several drugs have been proposed in the clinical scenario over the last years such as pioglitazone, vitamin E, liraglutide, sitagliptine, elafibranor, obeticholic acid, and pentoxifylline just to name a few. Also, much attention has been paid to the anti-inflammatory and lipid-lowering properties of other types of fats such as ω 3 polyunsaturated fatty acids (ω3 PUFA), which have long been investigated and showed positive impact on cardiovascular and hepatic alterations as well as in overall health.
Metabolic liver disease is currently a major cause of morbidity worldwide. Research on treatment strategies is in fact an interesting area to explore.
To determine the efficacy of hydroxy-fatty acids in experimental NAFLD/obesity as well as comparing the effects with diet switch regimen.
Histological analysis, western bloting analysis and α-mouse smooth muscle actin immunohistochemistry.
Mice treated with hydroxy-fatty acids 18-hydroxy-eicosapentaenoic acid (18-HEPE) and 17-hydroxy-docosahexaenoic acid (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 PPAR α/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.
Most serum metabolic parameters and histological features in obese mice are reversible by switching diet regimen from high-fat to low-fat for two wk. This finding supports the evidence of diet switch regimen as a valuable reference point for assessing alternative therapies. Finally, administration of 18-HEPE and 17-HDHA exerted hepatoprotective effects in the liver through up-regulation of nuclear receptors PPARα/γ and amelioration of serum adipokines profile.
Just as previous studies have reported, position of the alcohol group in both eicosapentaenoic acid and DHA is a relevant fact when it comes down to affinity for nuclear receptors. Importantly, these hydroxy-fatty acids originated from ω 3 PUFAs exert protective actions noticeable at the nanomolar ranges, many of which have been associated with the resolution of unremitting inflammation. A major proposed mechanism whereby these novel fatty acids exert anti-inflammatory actions is through enzymatic biotransformation into specialized pro-resolving mediators namely lipoxins, resolvins, protectins and maresins. However, since we did not explore this area, further analyses are required to elucidate these possible mechanisms.