Effects of resveratrol on HepG2 cells as revealed by (1)H-NMR based metabolic profiling.
BACKGROUND
Resveratrol, a polyphenol found in plant products, has been shown to regulate many cellular processes and to display multiple protective and therapeutic effects. Several in vitro and in vivo studies have demonstrated the influence of resveratrol on multiple intracellular targets that may regulate metabolic homeostasis.


METHODS
We analysed the metabolic modifications induced by resveratrol treatment in a human hepatoblastoma line, HepG2 cells, using a (1)H-NMR spectroscopy-based metabolomics approach that allows the simultaneous screening of multiple metabolic pathways.


RESULTS
Results demonstrated that cells cultured in the presence or absence of resveratrol displayed different metabolic profiles: the treatment induced a decreased utilisation of glucose and amino acids for purposes of energy production and synthesis associated to a decreased release of lactate in the culture medium and an increase in succinate utilisation. At the same time, resveratrol treatment slowed the cell cycle in the S phase without inducing apoptosis, and increased Sirt1 expression, also affecting its intracellular localisation.


CONCLUSIONS
Our results show that the metabolomic analysis of the exometabolome of resveratrol-treated HepG2 cells indicates a metabolic switch from glucose and amino acid utilisation to fat utilisation for the production of energy, and seem in agreement with an effect mediated via AMPK- and Sirt1-activation.


CONCLUSIONS
NMR-based metabolomics has been applied in a hepatocyte cell culture model in relation to resveratrol treatment; such an approach could be transferred to evaluate the effects of nutritional compounds with health impact.
Department of Basic and Applied Biology, University of L'Aquila, Via Vetoio, L'Aquila, Italy.
Mara
M
Massimi
Alberta
A
Tomassini
Fabio
F
Sciubba
Anatoli P
AP
Sobolev
Laura Conti
LC
Devirgiliis
Alfredo
A
Miccheli
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D055442:Metabolome; D055432:Metabolomics; D015999:Multivariate Analysis; D019906:Nuclear Magnetic Resonance, Biomolecular; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000096:biosynthesis; D013267:Stilbenes / Q000494:pharmacology*
D013267:Stilbenes; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol