Avocatin B Protects Against Lipotoxicity and Improves Insulin Sensitivity in Diet-Induced Obesity.

The effects of an avocado-derived fatty acid oxidation (FAO) inhibitor, avocatin B (AvoB), on glucose and lipid metabolism in models of diet-induced obesity (DIO) and in vitro models of lipotoxicity was evaluated. The safety of its oral consumption in humans was also determined.Mice were given high fat diets (HFD) for 8 weeks. Thereafter, AvoB or vehicle was administered orally twice weekly for 5 weeks. AvoB inhibited FAO which led to improved glucose tolerance, glucose utilization and insulin sensitivity. AvoB's effects on metabolism under lipotoxic conditions were evaluated in vitro in pancreatic β-islet cells and C2C12 myotubes. AvoB inhibited FAO and increased glucose oxidation resulting in lowering of mitochondrial reactive oxygen species that improved insulin responsiveness in C2C12 myotubes and insulin secretion in INS-1 (832/13) cells, respectively. A randomized, double-blind, placebo-controlled clinical trial in healthy human participants was conducted to assess the safety of AvoB consumption (50 mg or 200 mg/day for 60 days). AvoB was well-tolerated and not associated with any dose-limiting toxicity.Therapeutic agents that are safe and effectively inhibit FAO and improve DIO-associated pathologies are currently not available. AvoB's mechanism of action and favorable safety profile highlight its nutritional and clinical importance. This article is protected by copyright. All rights reserved.