Studies in animal models of diabetes and obesity have shown that resveratrol mitigates complications of metabolic diseases, beyond those resulting from oxidative stress. Furthermore, results obtained with cultured preadipocytes have also revealed that prolonged resveratrol treatment impairs adipogenesis. Considering the role of adipocytes in the hypertrophy of fat stores, and keeping in mind that insulin is the main trigger of excessive energy storage during post-prandial periods, the present study aimed to investigate how short-term effects of resveratrol can limit glucose disposal in a gut-adipose tissue axis. We found that resveratrol exhibits a more potent inhibitory capacity towards α-glucosidase than pancreatic lipase activity. Resveratrol also rapidly blunts glucose transport in mature fat cells by counteracting the effect of insulin and insulin-like lipogenic agents. Within two hours, resveratrol also inhibited the incorporation of glucose into lipids of adipocytes, which was unaffected by membrane cholesterol depletion. Moreover, the comparison between adipocytes with invalidated semicarbazide-sensitive amine oxidase activity and their control, or between resveratrol and several inhibitors, did not indicate that the recently described interaction of resveratrol with amine oxidases was involved in its antilipogenic effect. Caffeine and piceatannol, previously said to interact with glucose carriers, also inhibit lipogenesis in adipocytes, whereas other antioxidant phytochemicals do not reproduce such an antilipogenic effect. This study highlights the diverse first steps by which resveratrol impairs excessive fat accumulation, indicating that this natural molecule and its derivatives deserve further studies to develop their potential anti-obesity properties.
Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects.
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