Efectos del Acido a-lipoico sobre el metabolismo lipídico y la biogénesis mitocondrial en adipocitos: estudio de los mecanismos moleculares implicados
- Autores: Marta Fernández Galilea
- Directores de la Tesis: María Jesús Moreno Aliaga (dir. tes.), Patricia Pérez Matute (dir. tes.)
- Lectura: En la Universidad de Navarra ( España ) en 2013
- Idioma: español
- Tribunal Calificador de la Tesis: María Puy Portillo Baquedano (presid.), Matilde Bustos (secret.), Ricardo Rueda Cabrera (voc.), María Jose Iraburu Elizalde (voc.), Cedric Moro (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: Dadun
- Resumen
α-lipoic acid (5-(1,2-dithiolan-3-yl)-pentanoic acid) is a natural occurring compound which possesses antioxidant properties. Moreover, anti-obesity properties in both rodents and humans have been attributed to α-lipoic acid being adipose tissue a target for this compound. In this context, the present study has demonstrated the ability of α-LA to modulate lipid metabolism in both murine and human white adipocytes. Thus, α-LA: 1) Inhibits fatty acids uptake (through CD36 downregulation); 2) Reduces fatty acids esterification into triglycerides (through DGAT1 reduction); 3) Decreases de novo lipogenesis (induced by inhibition of FAS, SCD1 and ACC mediated by AMPK activation); 4) Stimulates lipolysis (mainly mediated by the phosphorylation of HSL through cAMP-mediated activation of PKA, probably through the inhibition of AdPLA and PGE2; 5) Increases fatty acid oxidation machinery (CPT1 and ACOX) in white adipocytes; 6) Promotes mitochondrial biogenesis by the activation of PGC-1α mediated by SIRT1 and AMPK activation; and 7) Induces a brown-like remodelling in white subcutaneous adipocytes from overweight/obese subjects.
Taking together all of these facts suggest that α-LA remodels adipocyte metabolism towards oxidation rather than storage, and this could contribute to the anti-obesity properties of α-LA.
