Ahmed 2019 Mol Nutr Food Res
|Ahmed N, Tcheng M, Roma A, Buraczynski M, Jayanth P, Rea K, Akhtar TA, Spagnuolo PA (2019) Avocatin B protects against lipotoxicity and improves insulin sensitivity in diet-induced obesity. Mol Nutr Food Res 63:e1900688.|
Abstract: 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.
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.
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.
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Obesity
Organism: Mouse, Rat Tissue;cell: Skeletal muscle, Islet cell;pancreas;thymus Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET Pathway: N, ROX HRR: Oxygraph-2k