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

Abstract

Obesity has become an epidemic concern in modern society. The chronic obesity is associated with metabolic disorders, such as hyperglycemia, hyperlipidemia, fatty liver, and cadiovascular disease, which cause high risk for mortality. The novel potential strategy to overcome obesity is to “burn out” the extra fat via “browning” of the white adipose tissues. The phytochemical resveratrol (Res) has attracted substantial attention due to its powerful amelioratory effects in metabolic diseases. However, how Res regulates the browning of adipose tissues remains largely elusive. Our data show that the NAD+‐dependent deacetylase silent information regulator 1 (Sirt1) mediates Res‐induced browning and fat reduction of adipocytes, as well as other Res‐improved metabolic phenotypes including hyperglycemina and hyperlipidemia in mice. Interestingly, we found that the major metabolites of Res in vivo (Res‐3‐O‐glucuronide, Res‐4′‐O‐glucuronide, and Res‐3‐O‐sulfate) were much less potent in promoting browning gene expressions and reducing fat content in comparison to Res itself in mouse and human adipocytes in vitro, suggesting the importance and necessarity to enhance the bioavailability of Res in vivo in consideration of therapeutic application. Taken together, our findings clarify the beneficial effects of Res on excess fat utilization via promotion of browning in a Sirt1‐dependent manner, suggesting the potential therapeutic application of Res in the treatment of obesity and related metabolic disorders.

Calorie Restriction and SIRT1 Overexpression Induce Different Gene Expression Profiles in White Adipose Tissue in Association with Metabolic Improvement

“…[48] It has been reported that CR and SIRT1 activation promote the recruitment of brown adipocytes within WAT, an effect that has been associated with improved glucose homeostasis. [49,50] Consistent with these reports, we found a remarkable induction of brown adipocyte-specific genes (i.e., Ucp1, Adrb3, or Cidea) in subcutaneous WAT of CR mice, whereas the effects of SIRT1 overexpression on the expression of these genes was very marginal or inexistent. Importantly, regardless of the effects on the mRNA levels of brown adipocyte-specific genes, we did not find any detectable UCP1 protein in WAT of CR and Sirt1-Tg mice, suggesting that browning of WAT was negligible.…”

Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway

“…Transmission electron microscopy showed that 3T3-L1 cells treated with BBR exhibited the characteristics of brown-like adipocytes with increased mitochondrial density and smaller lipid droplets (Figure 4 B). Previous studies have demonstrated that SIRT1 played an important role in energy metabolism and remodeling of adipose tissue 21 , 44 , 45 . We next elucidated whether SIRT1 is necessary for BBR to regulate the remodeling of adipose tissue.…”

Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice

“…Bars represent the mean ± SD. *P < 0.05 of cellular biochemical processes (Li et al, 2020;Liu et al, 2020;Wu et al, 2018;Zhang, Bi, et al, 2019). Mounting evidence indicated that SIRT1 could enhance the expression and transcriptional activity of Nrf2 to exert potent anti-oxidant effects (Huang et al, 2013).…”

“…SIRT1 might be involved in the mechanisms by which astaxanthin modulates Nrf2/Prx2/ASK1/p38 signalling after traumatic brain injury. SIRT1 is a type of histone deacetylase that regulates a variety of cellular biochemical processes (Li et al, 2020; Liu et al, 2020; Wu et al, 2018; Zhang, Bi, et al, 2019). Mounting evidence indicated that SIRT1 could enhance the expression and transcriptional activity of Nrf2 to exert potent anti‐oxidant effects (Huang et al, 2013).…”