Impact of dietary lipoic acid supplementation on liver mitochondrial bioenergetics and oxidative status on normally fed Wistar rats

Abstract

The aim of this study was to examine the effects of α-lipoic acid (α-LA) on liver mitochondrial bioenergetics and oxidative status for 8 weeks in normal-healthy animals. A pair-fed group was included to differentiate between α-LA direct effects and those changes due to reduced food intake. α-LA decreased body weight gain, liver weight and insulin levels with no differences compared to its pair-fed group. α-LA significantly reduced energy efficiency, the activity of the electron transport chain complexes and induced a lower efficiency of oxidative phosphorylation with reduced ATP production. α-LA supplementation directly decreased plasma triglycerides (TGs), free fatty acids and ketone bodies levels. A significant reduction in hepatic TG content was also observed. A significant up-regulation of Cpt1a, Acadl and Sirt3, all β-oxidation genes, along with a significant deacetylation of the forkhead transcription factor 3a (FOXO3A) was found in α-LA-treated animals. Thus, α-LA along with a standard chow diet has direct actions on lipid metabolism and liver by modulating mitochondrial function in normal-weight rats. These results should be taken into account when α-LA is administered or recommended to a healthy population.

Keywords:

• Lipoic acid
• healthy rats
• isocaloric standard chow diet
• liver
• mitochondria
• oxidative stress

Acknowledgements

The authors thank Ana Lorente and Verónica Ciaurriz for their technical assistance.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work has been supported by Línea especial “Nutrición, Obesidad y Salud” (University of Navarra LE/97) and Ministry of Science and Innovation (AGL2006-04716/ALI and AGL2009-10873/ALI). CIBER and RETICS networks are also gratefully credited.