Piceatannol prevents the progression of preadipocytes into fat-carrying adipocytes

Jeffrey Serrill, piceatannol, preadipocytes, adipogenesis, inhibition of obesity

The development of obesity has become an epidemic in the United States, with rates measured as high as 35% when the entire population is taken into account. The prevalence of obese individuals has roughly tripled since the 1960s, primarily as a result of poor diets and sedentary lifestyles. Thus, the identification and characterization of novel natural compounds which could prevent the progression of obesity is a top priority in many research labs and government health agencies. Recently, a study from Purdue University has suggested that the compound piceatannol may be of some benefit in this regard, and preliminary testing in culture models has revealed that this compound seems to promote the inhibition of adipogenesis. If this is indeed the case, a potential treatment for the development of obesity may not be that far off.

The term adipogenesis refers to the process through which mature fat storage cells are formed, subsequently forming “adipose tissue” which is used by the body as an energy reservoir, insulator, and hormone producer. This process is well understood, and involves several stages of cell differentiation; essentially, mesenchymal stem cells differentiate into preadipocytes (through regulation by a number of transcription factors), and then these preadipocytes, which are incapable of serving as fat reservoirs, differentiate into mature adipocytes through the actions of the PPAR-gamma nuclear receptor. Once formed, these mature adipocytes accumulate in certain regions of the body as adipose tissue. The signaling cascades which influence this development are very tightly synchronized, and dysregulation can ultimately result in an inordinate amount of fatty tissue in the body. This can result in obesity, which is an important risk factor for the subsequent onset of both cardiovascular disease and type 2 diabetes mellitus.

In the recent study, which was published in Journal of Biological Chemistry, the researchers gauged the ability of piceatannol, a compound found in red wine and grapes, to suppress the progression of adipogenesis. This compound (and the related compound resveratrol) has been previously found to have potential anti-carcinogenic and anti-inflammatory properties, though the specific nature of its possible beneficial effects on the development of obesity had not yet been established. In culture, the researchers demonstrated that, following treatment of preadipocytes with varying levels of piceatannol, the cells’ progression and differentiation into mature adipocytes was indeed disrupted, and that this inhibition seemed to occur during the early stages of normal cell cycling. Without mature adipocytes, the efficient storage of fats is not possible, a fact which makes these findings particularly relevant to the study of obesity.

Additionally, the research team investigated the ability of this compound to affect insulin signaling pathways in the context of adipogenesis, as these have also been shown to play an important role in the onset of adipocyte differentiation. As piceatannol has been previously shown to alter this pathway in aortic smooth muscle, it was thought that piceatannol may play a similar role in other cell types. As expected, it was shown that piceatannol has a significant inhibitory effect on insulin receptor activation by modulating the receptors’ ability to phosphorylate downstream signaling.

“Piceatannol actually alters the timing of gene expressions, gene functions and insulin action during adipogenesis, the process in which early stage fat cells become mature fat cells,” said Kee-Hong Kim, a professor of food science at Purdue University. “In the presence of piceatannol, you can see delay or complete inhibition of adipogenesis.”

Collectively, these results suggest that piceatannol may be a promising drug lead for the development of an anti-adipogenesis agent, though future studies will certainly need to demonstrate similar results in animal models. Nevertheless, these findings provide an exciting strategy for the prevention of adipogenesis through inhibition of the differentiation of preadipocytes into fat-sequestering tissue.

“These precursor cells, even though they have not accumulated lipids, have the potential to become fat cells,” Kim said. “We consider that adipogenesis is an important molecular target to delay or prevent fat cell accumulation and, hopefully, body fat mass gain.”

*All quotes and video taken from the Purdue University press release

For more information, see the original research article

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