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Tyrphostin AG17 inhibits adipocyte differentiation in vivo and in vitro
Camacho Morales, Alberto y Segoviano Ramírez, Juan Carlos y Sánchez García, Adriana y Herrera de la Rosa, José de Jesús y García Juárez, Jaime y Hernandez Puente, Carlos Alberto y Calvo Anguiano, Geovana y Maltos Uro, Sergio Rodolfo y Olguin, Alejandra y Gojon Romanillos, Gabriel y Gojon Zorrilla, Gabriel y Ortiz López, Rocío (2018) Tyrphostin AG17 inhibits adipocyte differentiation in vivo and in vitro. Lipids in Health and Disease, 17 (1). pp. 1-11. ISSN 1476-511X
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Resumen
Background: Excessive subcutaneous adiposity in obesity is associated to positive white adipocyte tissue (WAT) differentiation (adipogenesis) and WAT expandability. Here, we hypothesized that supplementation with the insulin inhibitor and mitochondrial uncoupler, Tyrphostin (T-AG17), in vitro and in vivo inhibits adipogenesis and adipocyte hypertrophy. Methods: We used a 3T3-L1 proadipocyte cell line to identify the potential effect of T-AG17 on adipocyte differentiation and fat accumulation in vitro. We evaluated the safety of T-AG17 and its effects on physiological and molecular metabolic parameters including hormonal profile, glucose levels, adipogenesis and adipocyte hypertrophy in a diet-induced obesity model using C57BL/6 mice. Results: We found that T-AG17 is effective in preventing adipogenesis and lipid synthesis in the 3T3-L1 cell line, as evidenced by a significant decrease in oil red staining (p <0.05). In obese C57BL/6 mice, oral administration of T-AG17 (0.175 mg/kg for 2 weeks) lead to decreased fat accumulation and WAT hypertrophy. Further, T-AG17 induced adipocyte apoptosis by activating caspase-3. In the hepatocytes of obese mice, T-AG17 promoted an increase in the size of lipid inclusions, which was accompanied by glycogen accumulation. T-AG17 did not alter serum biochemistry, including glucose, insulin, leptin, free fatty acids, creatinine, and aspartate aminotransferase. Conclusion: T-AG17 promotes adipocyte apoptosis in vivo and is an effective modulator of adipocyte differentiation and WAT hypertrophy in vitro and in vivo. Therefore, T-AG17 may be useful as a pharmacological obesity treatment.
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| Palabras claves no controlados: | Tyrphostin, AG17, Adipogenesis, Obesity, Hepatic steatosis, Oxidative phosphorylation, Thermogenesis, Mitochondrial uncoupling, Adipocyte differentiation | |||||||||||||||||||||||||||||||||||||||
| Materias: | Q Ciencia > QP Fisiología | |||||||||||||||||||||||||||||||||||||||
| Divisiones: | Medicina | |||||||||||||||||||||||||||||||||||||||
| Usuario depositante: | Lic. Josimar Pulido | |||||||||||||||||||||||||||||||||||||||
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| Fecha del depósito: | 18 Jun 2020 20:12 | |||||||||||||||||||||||||||||||||||||||
| Última modificación: | 28 Feb 2024 18:32 | |||||||||||||||||||||||||||||||||||||||
| URI: | http://eprints.uanl.mx/id/eprint/16231 |
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