Punica granatum L.-derived omega-5 nanoemulsion improves hepatic steatosis in mice fed a high fat diet by increasing fatty acid utilization in hepatocytes

K Zamora-López,I Escalona-Nández,S Tobón-Cornejo,A R Tovar,V Barbero-Becerra,A Estanes-Hernández,L G Noriega,C Pérez-Monter

doi:10.1038/s41598-020-71878-y

Abstract

Pomegranate seed oil (PSO) is mainly composed of punicic acid (PA), a polyunsaturated fatty acid also known as omega-5 (ω-5), a potent antioxidant associated with a variety of metabolic and cellular beneficial effects. However, the potential benefits of a nanoemulsified version of ω-5 (PSOn) have not been evaluated in a pathological liver condition. Here, we examined whether PSOn had beneficial effects on C57BL/6N mice fed a high-fat diet (HFD), specifically on hepatic steatosis. We observed that PSOn supplementation decreased body weight and body fat mass in control mice, whereas glucose intolerance, insulin resistance, energy expenditure, and hepatic steatosis were improved in both control mice and in mice fed a HFD. Interestingly, PSOn increased fatty acid oxidation in primary hepatocytes and antioxidant gene expression. Altogether, our data indicate that PSOn effectively reduces some of the HFD-derived metabolic syndrome indicators by means of an increase in fatty acid oxidation within hepatocytes.

Highlights

Pomegranate seed oil (PSO) is mainly composed of punicic acid (PA), a polyunsaturated fatty acid known as omega-5 (ω-5), a potent antioxidant associated with a variety of metabolic and cellular beneficial effects
We report that high-fat diet (HFD)-induced obese mice successfully improve their metabolic disturbances when treated with PSOn
We observed that only the control mice supplemented with PSOn (C-P) mice reduced this parameter when compared to a control mouse group, while this effect was not observed in mice under HFD supplemented with PSOn, neither from the beginning or when supplemented at week 76,9

Summary

Introduction

Pomegranate seed oil (PSO) is mainly composed of punicic acid (PA), a polyunsaturated fatty acid known as omega-5 (ω-5), a potent antioxidant associated with a variety of metabolic and cellular beneficial effects. While in human clinical trials, the antioxidant and anti-inflammatory effects of PA have been associated with a decrease in prostate-specific antigen (PSA) expression or lipid peroxidation, as well as a downregulation of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) aggregation, which might prevent cardiovascular events[17,18,19]. Colloidal silver nanoparticles of pomegranate peel extract, for example, had strong antioxidant, antibacterial, and anti-proliferative properties in vitro[20], while a nanoemulsified suspension of the seed oil (PSOn) was recently tested in a murine model of Creutzfeldt-Jakob disease (CJD) in order to assess its bioavailability, its activity against prion protein aggregation, and its effects on neurodegeneration-associated pathological features. Our study provides novel information concerning the use of PSOn as an alternative treatment to tackle metabolic syndrome and fatty liver disease

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