Bioprospection of rattlesnake venom peptide fractions with anti-adipose and anti-insulin resistance activity in vitro

Animal venoms are natural products that have served as a source of novel molecules that have inspired novel drugs for several diseases, including for metabolic diseases such as type-2 diabetes and obesity. From venoms, toxins such as exendin-4 (<i>Heloderma suspectum</i>) and crotamine (<i>Crotalus durissus terrificus</i>) have demonstrated their potential as treatments for obesity. Moreover, other toxins such as Phospholipases A₂ and Disintegrins have shown their potential to modulate insulin secretion in vitro. This suggests an unexplored diversity of venom peptides with a potential anti-obesogenic in Mexican rattlesnake venoms. For that reason, this study explored the in vitro effect of Crotalus venom peptide-rich fractions on models for insulin resistance, adipocyte lipid accumulation, antioxidant activity, and inflammation process through nitric oxide production inhibition. Our results demonstrated that the peptide-rich fractions of <i>C. aquilus, C. ravus</i>, and <i>C. scutulatus scutulatus</i> were capable of reverting insulin resistance, enhancing glucose consumption to normal control; <i>C. culminatus, C. molossus oaxacus</i>, and <i>C. polystictus</i> diminished the lipid accumulation on adipocytes by 20%; <i>C. aquilus, C. ravus</i>, and <i>C. s. salvini</i> had the most significant cellular antioxidant activity, having nearly 80% of ROS inhibition. <i>C. aquilus, C. pyrrhus,</i> and <i>C. s. salvini</i> inhibited nitric oxide production by about 85%. We demonstrated the potential of these peptides from <i>Crotalus</i> venoms to develop novel drugs to treat type-2 diabetes and obesity. Moreover, we described for the first time that <i>Crotalus</i> venom peptide fractions have antioxidant and inflammatory properties in vitro models.