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.
The biomedical potential of the edible red seaweed Agarophyton chilense (former Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPAR{gamma} nuclear receptor. PPAR{gamma} is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. TZDs medical use is limited due to undesired side effects, the fact that it has triggered the search for partial agonists without the TZDs side effects. We produced A.chilense oleoresin (Gracilex(R)) that induces the activation of PPAR{gamma} without inducing adipocyte differentiation, similar to PPAR{gamma} partial agonists. In a model of high-fat diet-induced obesity in male mice, we showed that treatment with Gracilex(R) improves insulin sensitivity, normalizing altered glucose and insulin parameters. Gracilex(R) was enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as {beta}-carotene and tocopherols. Gracilex(R) possesses antioxidant activity in vitro (CUPRAC) and increased the antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex(R) is an excellent source of healthy lipids targeting PPAR{gamma} with antioxidant activity and a high nutraceutical value.