June 2013

Butein and adipogenesis: a new compound for combating fat

Butein’s signaling cascade 
Butein’s signaling cascade
Credit for flower: F.A. Barkley
Credit for signaling cascade: adapted from Song et al., J. Lipid Res. 5: 1385 – 1396 (2013).

If the statistics are any indication of our standing in the battle against the bulge, it’s pretty clear that we are losing and adipogenesis is winning.
 
Adipogenesis, also known as adipocyte differentiation, is the development of fat cells called adipocytes from preadipocytes.
 
Scientists recently uncovered the anti-adipogenic effects of the natural compound butein and reported their findings in the Journal of Lipid Research (1).
 
Butein is found in the extracts of Rhus verniciflua Stokes (or RVS), a tree that has been used as a food additive and traditional herbal medicine in eastern Asia (2, 3).
 
Researchers first isolated and identified butein from RVS using fractionation, chromatography and nuclear magnetic resonance techniques. Adipocyte differentiation was induced in mouse cell lines using an adipogenic cocktail that activates several key genes required for adipogenesis to occur. Upon differentiation, cells were treated with isolated butein to assess its biological effects on the process.
 
Butein was confirmed as a bona fide anti-adipogenic compound based on its ability to suppress lipid accumulation and decrease the expression of key adipogenic markers such as CCAAT/enhancer-binding protein, peroxisome proliferator-activated receptor γ and adipocyte fatty acid binding protein 2. Interestingly, it exhibited these anti-adipogenic properties at lower doses than both resveratrol and genistein, two well-known anti-adipogenic compounds (4, 5, 6, 7).
 
To gain further insight into the mechanism of butein’s anti-adipogenic effects, several signaling pathways involved in adipogenesis, namely signal transducer and activator of transcription 3 and transforming growth factor-β, were investigated.
 
An analysis of temporal expression profiles of STAT3 and TGF-β target genes revealed that butein exerts its anti-adipogenic effects by stimulating TGF-β signaling, which leads to the inhibition of STAT3. Notably, the expression of the same STAT3 target genes was not affected by resveratrol, suggesting that the biological action of butein is specific and unique.
 
“One may speculate that the combination of these two anti-adipogenic compounds can exert additive effects in anti-adipogenesis through … distinct molecular mechanisms,” says Kye Won Park, associate professor of food science and biotechnology at Sungkyunkwan University and lead researcher in the study. “It will be interesting to investigate … TGF-β or STAT3 signaling … in lipid accumulation and its related diseases.”
 
University of California, Los Angeles, professor and prominent adipocyte biology researcher Peter Tontonoz (not involved in the study) echoes this sentiment: “It will be interesting to address how modification of the TGF-β and STAT3 (signaling pathways) may affect adipocyte biology in animals,” says the scientist.
 
Luckily, this is the path forward for the researchers involved in the study, who plan to elucidate the in vivo effects and exact molecular target or targets of butein in the near future.
 
Obesity is a major public health concern. More than two-thirds of U.S. adults are considered to be overweight or obese (8), and the epidemic is quickly becoming a global issue.

It’s officially been a year since Nature’s Pathways launched. My, how time flies! I’ve highlighted the biological activity of a variety of natural products — from the antiarthritic effects of the Chinese herb celastrus to the sedative effects of valerian. The goal of the column has been quite simple: to serve as a place where good science and practicality converge. Hopefully you’ve found the research presented both informative and interesting. Thanks for reading!

As individuals become obese, their adipocytes enlarge and cause molecular and cellular alterations such as an increase in lipid accumulation and the dysregulation of TGF-β and STAT3 signaling. These changes affect whole-body metabolism and are known to be involved in the pathogenesis of a variety of metabolic diseases, including Type 2 diabetes, cardiovascular disease, hypertension, stroke and some forms of cancer (9, 10). Hence, understanding the origin and development of adipocytes may be critical to the analysis and treatment of many chronic diseases.

 

REFERENCES
  1.   1.  Song et al., J. Lipid Res. 5: 1385 – 1396 (2013).
  2.   2.  Gamble, A. et al. Chinese Herbal Medicine: Materia Medica, Eastland Press (1993).
  3.   3.  Yoo, H.T. et al. Compendium of prescriptions from the countryside Hyangyakjipseongbang 1433: 640 (1977).
  4.   4.  Baur , J.A. et al. Nature 444: 337 – 342 (2006).
  5.   5.  Feige , J.N. et al. Cell Metab. 8: 347 – 358 (2008).
  6.   6.  Hung , P.F. et al. Am. J. Physiol. Cell Physiol. 288: C1094 – C1108 (2005).
  7.   7.  Flegal, K.M. et al. Journal of the American Medical Association. 5: 491 – 97 (2012).
  8.   8.  Hwang , J.T. et al. Biochem. Biophys. Res. Commun. 338: 694 – 699 (2005).
  9.   9.  World Health Organization fact sheet: obesity and overweight. 
  10. 10.  Mokdad, A.H. et al. JAMA 289: 76 – 9 (2003).

Shannadora HollisShannadora Hollis (sholl002@umaryland.edu) received her B.S. in chemical engineering from North Carolina State University and is a Ph.D. student in the molecular medicine program at the University of Maryland, Baltimore. Her research focuses on the molecular mechanisms that control salt balance and blood pressure in health and disease. She is a native of Washington, D.C., and in her spare time enjoys cooking, thrift-store shopping and painting.

 

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