Abstract

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.

Highlights

  • The potential benefits of resveratrol in treating metabolic diseases have been claimed by numerous researchers in the past decade

  • Considering we have previously reported that phenelzine, a monoamine oxidase (MAO) and SSAO inhibitor, inhibits lipogenesis in mouse fat cells [28] in an apparently similar manner to that of resveratrol [29], it appeared crucial to test resveratrol in fat cells with invalidated SSAO and to compare its antilipogenic effect to several related pharmacologic agents

  • Our approach confirmed that all of the antilipogenic effects of resveratrol-prolonged treatments reported in obese rodents could be summarized in short-term in vitro experiments, performed with mature adipocytes

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Summary

Introduction

The potential benefits of resveratrol in treating metabolic diseases have been claimed by numerous researchers in the past decade (for reviews, see [1,2,3]). The observations made on animal models of obesity have resulted in poorly effective clinical applications of resveratrol [4,5,6]. Antioxidants 2019, 8, 74 same time, the recently developed incretin receptor dual agonists, mimicking both glucagon-like peptide 1 and glucose-dependent insulinotropic peptide effects, are successfully decreasing both hyperglycaemia and body mass in obese and diabetic patients in current clinical trials [7]. Resveratrol is still one of the most widely studied polyphenols in the field of obesity and diabetes [11]. An increasing number of studies deal with the anti-obesity properties of other phytochemicals, which are expected to be more successfully extrapolated to humans, resveratrol remains a reference regarding the beneficial effects of polyphenols for treating metabolic diseases

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