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La lipasa de triglicéridos adiposos contribuye a la caquexia asociada al cáncer
Suman K Das1, Sandra Eder, Silvia Schauer
1Institute of Pathology, Medical University of Graz, Graz, Austria.
Science (New York, N.Y.)
|June 18, 2011
Resumen
La inhibición de la lipólisis, la descomposición de la grasa, puede prevenir la caquexia asociada al cáncer. La eliminación genética de las lipasas clave protegió a los ratones de la pérdida de músculo y grasa, lo que sugiere nuevos objetivos terapéuticos.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Oncología Oncología.
- Fisiología Fisiología Fisiología.
Sus antecedentes:
- La caquexia es un síndrome de desgaste complejo común en pacientes con cáncer, marcado por una pérdida significativa de tejido muscular y graso.
- La caquexia asociada al cáncer (CAC) presenta un gran desafío clínico, que afecta el pronóstico del paciente y la calidad de vida.
Objetivo del estudio:
- Para investigar el papel de la lipólisis en el desarrollo de la caquexia asociada al cáncer.
- Para determinar si la inhibición de la lipólisis puede mejorar los síntomas de CAC.
Principales métodos:
- Se utilizaron modelos de ratón, incluidos ratones salvajes C57BL/6 y ratones genéticamente modificados que carecen de lipasa triglicérida adiposa (Atgl) o lipasa sensible a las hormonas (Hsl).
- Tumores inducidos en ratones mediante la inyección de células de carcinoma de pulmón de Lewis o células de melanoma B16.
- Se evaluaron los cambios en la masa del tejido adiposo blanco (TAB), la apoptosis de los miocitos y la degradación del músculo proteasoma.
Principales resultados:
- Los ratones con tumores con deficiencia de Atgl mostraron resistencia a la lipólisis de WAT, una reducción de la apoptosis de los miocitos y una menor degradación del músculo proteasómico, preservando la masa adiposa y muscular.
- Los ratones con deficiencia de Hsl también exhibieron protección contra la caquexia, aunque en menor medida que los ratones con deficiencia de Atgl.
- Estos hallazgos demuestran que la lipólisis funcional es crítica para la patogénesis de CAC.
Conclusiones:
- La lipólisis es una vía esencial en el desarrollo de la caquexia asociada al cáncer.
- Dirigirse farmacológicamente a las lipasas metabólicas presenta una estrategia terapéutica potencial para prevenir o tratar la caquexia en pacientes con cáncer.
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