Avocatin B Protects Against Lipotoxicity and Improves Insulin Sensitivity in Diet‐Induced Obesity
| Autor: | Paul A. Spagnuolo, Tariq A. Akhtar, Alessia Roma, Michael Buraczynski, Nawaz Ahmed, Preethi Jayanth, Kevin A Rea, Matthew Tcheng |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_treatment Pilot Projects Pharmacology Diet High-Fat 03 medical and health sciences Double-Blind Method Insulin-Secreting Cells Animals Humans Insulin Medicine Obesity Muscle Skeletal Beta oxidation chemistry.chemical_classification Reactive oxygen species 030109 nutrition & dietetics Persea business.industry Fatty Acids Lipid metabolism Metabolism Lipids 3. Good health Mice Inbred C57BL 030104 developmental biology chemistry Lipotoxicity Mechanism of action Toxicity Female Insulin Resistance medicine.symptom business Food Science Biotechnology |
| Zdroj: | Molecular Nutrition & Food Research. 63:1900688 |
| ISSN: | 1613-4133 1613-4125 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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