Characterization of an Agarophyton chilense Oleoresin Containing PPARγ Natural Ligands with Insulin-Sensitizing Effects in a C57Bl/6J Mouse Model of Diet-Induced Obesity and Antioxidant Activity in Caenorhabditis elegans.

Claudio Pinto,Luisa León,Yasmin Salvatore,Carla González,Víctor Barraza,Rebeca Aldunate,Francisco Castañeda,Karen Fuenzalida,María Raquel Ibáñez,Gloria Loyola,Francisca C Bronfman,Loretto Contreras-Porcia

doi:10.3390/nu13061828

Abstract

The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex® improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex® is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and β-carotene. Accordingly, Gracilex® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.

Highlights

The edible Chilean red macroalgae Agarophyton chilense [1], commonly known as “pelillo”, has been used as a food and medicinal herb since pre-Hispanic times in Chile, as indicated by findings at the archaeological site of MonteVerde (~14,000 years ago) [2]
Our results indicate that Gracilex® contains PPARγ activators acting as partial agonists, since they do not induce adipocyte differentiation like the TZD rosiglitazone
To further confirm the activation of PPARγ by lipids derived from Gracilex® and to study the contribution of PPARγ to the increased luciferase, we assessed the ability of Gracilex® to activate the chimeric GAL4-DBD-peroxisome proliferator-activated receptors (PPARs)-LBD protein from a Gal4-dependent MH100-Luc reporter using PC12 cells (Figure 1B)

Summary

Introduction

The edible Chilean red macroalgae Agarophyton chilense (formerly Gracilaria chilensis) [1], commonly known as “pelillo”, has been used as a food and medicinal herb since pre-Hispanic times in Chile, as indicated by findings at the archaeological site of MonteVerde (~14,000 years ago) [2]. In recent years, there has been increased interest in identifying novel bioactive compounds that demonstrate health benefits to confirm and increase the added value of edible red seaweeds [8,11]. Red algae such as A. chilense are an excellent source of healthy essential fatty acids such as polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, arachidonic acid, and oleic, linoleic, and α-linolenic fatty acids. In the Gracilaria genus, lipid extraction has revealed a complex lipid composition of glycerolipids and omega-3 and omega-6 PUFAs and their oxidized derivatives, known as oxylipins [12,13,14,15]. The oxylipin structure is similar or equivalent to that of mammalian prostaglandins, leukotrienes, and eicosanoids [19], which are well-known ligands of peroxisome proliferator-activated receptors (PPARs) [20,21,22]

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