Resveratrol and Its Human Metabolites—Effects on Metabolic Health and Obesity

Abstract

Resveratrol is one of the most widely studied polyphenols and it has been assigned a plethora of metabolic effects with potential health benefits. Given its low bioavailability and extensive metabolism, clinical studies using resveratrol have not always replicated in vitro observations. In this review, we discuss human metabolism and biotransformation of resveratrol, and reported molecular mechanisms of action, within the context of metabolic health and obesity. Resveratrol has been described as mimicking caloric restriction, leading to improved exercise performance and insulin sensitivity (increasing energy expenditure), as well as having a body fat-lowering effect by inhibiting adipogenesis, and increasing lipid mobilization in adipose tissue. These multi-organ effects place resveratrol as an anti-obesity bioactive of potential therapeutic use.

Resveratrol promotes white adipocytes browning and improves metabolic disorders in Sirt1‐dependent manner in mice

“…37 Once Res enters the gastrointestinal tract, most was proccessed through enterocytes of small intestine, 38 in which the molecule was conjugated with sulfate or glucuronate by sulfotransferases or uridine 5′-diphospho-glucuronosyltransferases (UGTs), repectively, 39,40 with distribution into different organs, leading to consequences for its bioavailability and activity. 30 Though some studies on Res metabolites showed effect on autophagy, 41,42 as shown in our data and other studies, 43,44 these metabolites had less effect compared with its origin form on metabolism. In the current study, Res metabolites were applied in insulin resistant 3T3-L1 adipocyte to explore their potential effects.…”

“…Furthermore, controversy may be partially attributed to nonphysiological concentrations used and resveratrol metabolites . Once Res enters the gastrointestinal tract, most was proccessed through enterocytes of small intestine, in which the molecule was conjugated with sulfate or glucuronate by sulfotransferases or uridine 5′‐diphospho‐glucuronosyltransferases (UGTs), repectively, with distribution into different organs, leading to consequences for its bioavailability and activity . Though some studies on Res metabolites showed effect on autophagy, as shown in our data and other studies, these metabolites had less effect compared with its origin form on metabolism.…”

“…Despite the striking beneficial effects of Res in regulation of metabolic parameters in obese rodent model, it remains controversial whether Res exerts robust effects on humans under physiological dose application. 30 In other words, the dose used in mice may be theoretically beyond the pharmacological dose in humans. The relative poor bioavailability of Res is mostly due to its low water solubility and rapid metabolism in vivo.…”

“…The major metabolites of Res in vivo are Res sulfate and glucuronide conjugates. 30 To test the effects of Res metabolites in regulation of fat metabolism, we treated the insulin resistant mouse adipocytes with 10 μM of Res or its different metabolites (Res-3-O-glucuronide, Res-4′-O-glucuronide, and Res-3-O-sulfate). Our data ( Figure 6A-C) showed that: (1) Res-3-O-glucuronide and Res-4′-O-glucuronide were able to reduce the fat content, increase the mRNA levels of Sirt1, ATGL, UCP1, PRDM16, TMEM26, and CIDEA, and decrease the mRNA levels of PPARγ; (2) the magnitudes of Res-3-O-glucuronide and Res-4′-O-glucuronide in these regulations were consistently less powerful than Res treatment itself; (3) Res-3-O-sulfate failed to alter fat metabolism and gene expressions.…”

Myeloid-derived suppressor cells—new and exciting players in lung cancer

“…Resveratrol (RSV) is a pleiotropic phytochemical found in peanuts and grapes that has been indicated to provide a wide range of health benefits, such as reducing oxidative, inflammatory, and apoptotic signals [122]-protecting against neurological decline [123], improving cardiovascular health [124], ameliorating diabetes [125], and preventing cancer [126]. The anticancer properties of RSV act through diverse molecular mechanisms that have been investigated in a plethora of cellular and animal models [127,128]…”