Resveratrol Improves Adipose Insulin Signaling and Reduces the Inflammatory Response in Adipose Tissue of Rhesus Monkeys on High-Fat, High-Sugar Diet

Abstract

SUMMARY Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here we tested the effect of a 2-year resveratrol administration on pro-inflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Eighty mg/day of resveratrol for 12-month followed by 480 mg/day for the second year decreased adipocyte size, increased sirtuin 1 expression, decreased NF-κB activation and improved insulin sensitivity in visceral but not subcutaneous WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS +/− resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys.

Resveratrol and SRT1720 Elicit Differential Effects in Metabolic Organs and Modulate Systemic Parameters Independently of Skeletal Muscle Peroxisome Proliferator-activated Receptor γ Co-activator 1α (PGC-1α)

“…Both RSV-S and RSV-L groups displayed increased transcription of mitochondrial genes, enhanced adiponectin expression, and reduced adipose tissue inflammation. These effects of RSV have also been observed in other studies with both rodents (37-39) and non-human primates (40). In search of a mechanism for how RSV mediates these effects, we could show that RSV treatment resulted in a reduced phosphorylation of CREB in WAT, correlating with a reduced transcrip-tion of ATF3.…”

Effect of resveratrol on visceral white adipose tissue inflammation and insulin sensitivity in a mouse model of sleep apnea

“…However, chronic SF induces increases in central nervous system levels of TNF-α (6), such that it is likely that the increases in macrophage release of this pro-inflammatory cytokine in SF-exposed mice may reflect an overall systemic inflammatory response induced by the disrupted sleep paradigm. In this setting, Resv administration normalized TNF-α VWAT macrophage release, suggesting that this compound exerts anti-inflammatory effects on adipose tissue, as previously inferred by several investigators (19)(20)(21)(22)(23). Secondly, we opted not to impose a high fat diet regimen or to employ transgenic mice with heightened susceptibility to obesity, since we wished to examine the isolated effects of Resv on SF-induced metabolic dysfunction and obesogenic behaviors.…”

Metabolic effects of resveratrol: addressing the controversies

“…Sirt1 activation can also modulate several stress response transcription factors including hypoxia-inducible factors and FOXO1, FOXO3, and FOXO4 [123][124][125][126][127]. In rhesus monkeys, resveratrol reduced inflammation in the white adipose tissue of animals fed a high fat/high sugar diet [112]. In a mouse model of Crohn's disease, resveratrol reduced inflammatory cytokines [128].…”