Efectos del Acido a-lipoico sobre el metabolismo lipídico y la biogénesis mitocondrial en adipocitosestudio de los mecanismos moleculares implicados

  1. Fernández Galilea, Marta
Dirigida por:
  1. María Jesús Moreno Aliaga Directora
  2. Patricia Pérez Matute Director/a

Universidad de defensa: Universidad de Navarra

Fecha de defensa: 18 de diciembre de 2013

Tribunal:
  1. María Puy Portillo Baquedano Presidente/a
  2. Matilde Bustos Secretario/a
  3. Ricardo Rueda Cabrera Vocal
  4. Cedric Moro Vocal
  5. María Jose Iraburu Elizalde Vocal
Departamento:
  1. (FFN) Ciencias de la Alimentación y Fisiología

Tipo: Tesis

Teseo: 116261 DIALNET lock_openDadun editor

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.