Caffeine dose-dependently induces thermogenesis but restores ATP in HepG2 cells in culture.
Caffeine has been hypothesised as a thermogenic agent that might help to maintain a healthy body weight. Since very little is known about its actions on cellular energy metabolism, we investigated the effect of caffeine on mitochondrial oxidative phosphorylation, cellular energy supply and thermogenesis in HepG2 cells, and studied its action on fatty acid uptake and lipid accumulation in 3T3-L1 adipocytes at concentrations ranging from 30-1500 μM. In HepG2 cells, caffeine induced a depolarisation of the inner mitochondrial membrane, a feature of mitochondrial thermogenesis, both directly and after 24 h incubation. Increased concentrations of uncoupling protein-2 (UCP-2) also indicated a thermogenic activity of caffeine. Energy generating pathways, such as mitochondrial respiration, fatty acid oxidation and anaerobic lactate production, were attenuated by caffeine treatment. Nevertheless, HepG2 cells demonstrated a higher energy charge potential after exposure to caffeine that might result from energy restoration through attenuation of energy consuming pathways, as typically found in hibernating animals. In 3T3-L1 cells, in contrast, caffeine increased fatty acid uptake, but did not affect lipid accumulation. We provide evidence that caffeine stimulates thermogenesis but concomitantly causes energy restoration that may compensate enhanced energy expenditure.
Department of Nutritional and Physiological Chemistry, University of Vienna, Vienna, Austria.
Annett
A
Riedel
Marc
M
Pignitter
Christina M
CM
Hochkogler
Barbara
B
Rohm
Jessica
J
Walker
Gerhard
G
Bytof
Ingo
I
Lantz
Veronika
V
Somoza
D041721:3T3-L1 Cells; D000255:Adenosine Triphosphate / Q000378:metabolism*; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002110:Caffeine / Q000494:pharmacology*; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D056945:Hep G2 Cells; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D000071246:Uncoupling Protein 2
D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D019344:Lactic Acid; D002110:Caffeine; D000255:Adenosine Triphosphate