Researchers from the University of Texas found that the antioxidant compound resveratrol stimulates the expression of adiponectin – a hormone released from fat cells, which plays an important role in the regulation of insulin sensitivity and energy
The new study, published in the Journal of Biological Chemistry, reports that resveratrol stimulates the expression and protein clustering (multimerization) of adiponectin in specialized fat cells through the activation of a protein known as disulfide bond-A oxidoreductase- like protein (DsbA-L).
“Our study uncovers a novel mechanism by which resveratrol exerts its health beneficial effect,” said senior author Dr Feng Liu, professor of pharmacology at UT.
“The results from these studies should be of interest to those who are obese, diabetic and growing older,” he added.
They said the finding that resveratrol promotes adiponectin expression provides a novel mechanism by which resveratrol exerts its health beneficial functions.
Anti-oxidant
Resveratrol – a powerful polyphenol and anti-fungal chemical – is often hyped as the major bioactive compound in grapes and red wine – and has particularly been associated with the so-called 'French Paradox' which describes the low incidence of heart disease and obesity among the French; despite their relatively high-fat diet and levels of wine consumption.
Interest in the compound exploded in 2003 when research from David Sinclair and his team from Harvard reported that resveratrol was able to increase the lifespan of yeast cells. The research, published in Nature, was greeted with international media fanfare and ignited flames of hope for an anti-ageing pill.
According to Sinclair’s findings, resveratrol activated a gene called sirtuin1 (Sirt1), which is also activated during calorie restriction in various species, including humans.
However, recent studies have suggested that resveratrol may exert its beneficial functions via Sirt1-independent mechanisms.
Professor Liu said that adiponectin has a wide range of beneficial effects on obesity-related medical complications, and noted that both adiponectin and resveratrol display anti-obesity, anti-insulin resistance and anti-aging properties.
Whilst recent research has identified that the expression DsbA-L – a protein that is known to regulate the expression of adiponectin – is significantly reduced in obese human subjects and mice.
Novel mechanism
The researchers reported that resveratrol significantly enhanced the levels of DsbA-L in animal cells.
Prof Liu told NutraIngredients-USA.com that this suggests that the promoting effects of resveratrol on adiponectin multimerization and expression are mainly mediated by up-regulating DsbA-L.
The researchers reported that the stimulatory effect of resveratrol was not affected by knocking out Sirt1 – thus confirming a novel, Sirt1 independent mechanism for the actions of resveratrol – but was reduced by the suppression of DsbA-L expression.
Critical role
“We have shown that resveratrol plays a positive role in regulating adiponectin expression and multimerization in adipocytes via a Sirt1-independent mechanism,” said the researchers.
They added that DsbA-L plays “a critical role” in promoting the effects of resveratrol on adiponectin, which in turn provides beneficial metabolic effects.
Prof Liu said that the discovery of such a novel mechanism for the benefits of resveratrol may help in the development of therapeutic treatments for metabolic diseases, but added that further research is needed to quantify any dose / response relationship between resveratrol intake and DsbA-L and adiponectin activation.
Source: Journal of Biological Chemistry
Published online ahead of print, 10.1074/jbc.M110.188144
“Up-regulation of Adiponectin by Resveratrol: The essential roles of the Akt/Fox01 and AMP-activated protein kinase signaling pathways and DsbA-L”
Authors: A. Wang, M. Liu, X. Liu, L.Q. Dong, R.D. Glickman, T.J. Slaga, Z. Zhou, F. Liu