Resveratrol and genistein as adenosine triphosphate–depleting agents in fat cells

Resveratrol and genistein are plant-derived compounds known to exert pleiotropic effects in many cell types, including adipocytes. However, the effects of these compounds on the energetic status of fat cells are unknown. The present study aimed to determine whether resveratrol and genistein influence adenosine triphosphate (ATP) levels in freshly isolated rat adipocytes. To determine the effects of resveratrol and genistein on adipocyte ATP content, cells were exposed to insulin and glucose or insulin and alanine without tested compounds or with 6.25 to 50 μmol/L resveratrol or genistein. Resveratrol substantially reduced glucose- and alanine-derived ATP in adipocytes. This was not due to the inhibition of glucose transport because the influence of the test compound on insulin-stimulated glucose uptake by adipocytes appeared to be stimulatory. Moreover, resveratrol reduced both alanine oxidation and mitochondrial membrane hyperpolarization. It was also demonstrated that preincubation of cells with resveratrol slightly diminished ATP levels despite the withdrawal of the tested compound from the buffer. The genistein effect was accompanied by attenuation of the mitochondrial membrane hyperpolarization. The compound failed to significantly affect insulin-stimulated glucose uptake by fat cells. Similarly to resveratrol, preincubation of adipocytes with genistein slightly reduced ATP in cells exposed to glucose and insulin. Results of the present study revealed the potent ability of resveratrol to reduce ATP in rat adipocytes, whereas genistein appeared to be less effective. It is suggested that both tested compounds diminish adipocyte ATP via attenuation of the metabolic activity of mitochondria. Because numerous cellular events are strongly ATP dependent, the ATP-depleting effects of resveratrol and genistein may have pleiotropic consequences for adipocyte functions.