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

• Published in: Molecular nutrition & food research 2019-12, Vol.63 (24), p.e1900688-n/a
• Main Authors: Ahmed, Nawaz, Tcheng, Matthew, Roma, Alessia, Buraczynski, Michael, Jayanth, Preethi, Rea, Kevin, Akhtar, Tariq A., Spagnuolo, Paul A.
• Format: Article
• Language: English
• Subjects: avocados; Chemical compounds; Clinical trials; Consumption; Diet; Evaluation; fatty acid oxidation; Fatty acids; Glucose; Glucose metabolism; Glucose tolerance; High fat diet; high‐fat diets; Insulin; Insulin secretion; Islet cells; Lipid metabolism; Lipids; Metabolism; Mitochondria; Myotubes; Obesity; Oral administration; Oxidation; Pancreas; Pharmacology; polyhydroxylated fatty alcohols; Reactive oxygen species; Safety; Sensitivity analysis; Toxicity
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201900688

Scope 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 are evaluated. The safety of its oral consumption in humans is also determined. Methods and results Mice are given high‐fat diets (HFD) for 8 weeks. Thereafter, AvoB or vehicle is administered orally twice weekly for 5 weeks. AvoB inhibits FAO which led to improved glucose tolerance, glucose utilization, and insulin sensitivity. AvoB's effects on metabolism under lipotoxic conditions are evaluated in vitro in pancreatic β‐islet cells and C2C12 myotubes. AvoB inhibits FAO and increases glucose oxidation, resulting in lowering of mitochondrial reactive oxygen species that improves 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 is conducted to assess the safety of AvoB consumption (50 mg or 200 mg per day for 60 days). AvoB is well‐tolerated and not associated with any dose‐limiting toxicity. Conclusion 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. Avocatin B, an avocado derived fatty acid oxidation inhibitor, reverses lipotoxicity and mitochondrial dysfunction in mice on high‐fat diets, thereby slowing weight gain and improving glucose metabolism in skeletal muscle and the pancreas. Avocatin B is also well tolerated in healthy human participants after 60 days of consumption.