Mammals have two types of fat tissue: Brown Adipose Tissue (BAT or “brown fat”) and White Adipose Tissue (WAT or “white fat”). Brown fat cells are packed with many small fat droplets and mitochondria, which is why they appear “brown” under the microscope. Their mitochondria contain high levels of the protein UCP-1 (uncoupling protein 1), which “uncouples” fat metabolism from the generation of chemical energy molecules (ATP) for the cell. Instead, brown fat cells release the energy contained in the fat in the form of heat. This explains why brown fat is primarily found in hibernating animals or in newborns that need to generate heat. They burn their fat to maintain their body temperature. White fat, on the other hand, cannot be burned off so easily and also seems to responsible for many of the deleterious effects associated with obesity, such as diabetes and inflammation.
Recent studies in humans have shown that even adult humans have small stores of brown fat, primarily located in the neck or near big blood vessels. Occasional small islands of brown fat cells can be found amid the large white fat tissue in the adult. Since brown fat is generally considered to be much healthier than white fat, scientists have tried to develop methods to convert white fat into brown fat. Some have used genetic approaches in mouse models of obesity, others have exposed human subjects to a few hours of cold temperatures. The paper “Increased cGMP promotes healthy expansion and browning of white adipose tissue” published in the FASEB Journal by Michaela Mitschke and colleagues (Online publication January 9, 2013) uses a rather unusual approach to induce the “browning” of white fat.
The researchers treated mice with Viagra (sildenafil), a drug that is normally used for erectile dysfunction. They found that only seven days of Viagra treatment increased the levels of the brown fat protein UCP-1 and that the white fat began showing the presence of “beige” (not quite white and not fully brown) fat. The choice of Viagra was not quite arbitrary, because they also showed that cultured fat cells contain cGMP-dependent protein kinase I (PKGI), which is part of the signaling pathway targeted by Viagra, and that increasing the levels of PKGI converted these cells into thermogenic brown fat cells. The researchers did not observe any weight loss in the mice, but they attributed this to the fact that they purposefully chose a very short treatment time in order to investigate fat conversion in the absence of fat loss. Their data suggests that longer treatment would lead to even more white-to-brown conversion of fat and to an actual weight loss, because the generated “beige” or brown-like fat cells could be easily burned off. A prior study that treated mice for 12 weeks with Viagra did indeed show some evidence of weight loss with Viagra treatment.
This new study is quite interesting and may have important practical implications because it uses an approved drug that is commonly available for human studies. Treating obese patients with Viagra would be much easier than trying to genetically convert their white fat to brown fat or to expose them to long periods of cold. However, overweight people should not expect that “Super-Size” orders at their favorite fast food joint will come with a Viagra pill. They also should not run to their physicians to ask for Viagra prescriptions at this point. One has to bear in mind that there are a number of caveats when trying to apply these findings in mice to humans. Chronic Viagra treatment in humans may be associated with some significant side effects and there is no consensus that “browning” of fat in adult humans will necessarily improve their health. Most of the data on the benefits of creating brown fat are based on animal studies. We therefore still need to await future studies, both in animals and in humans, that study the impact of long-term Viagra treatment on weight loss and associated health benefits as well as potential side effects, before definitive conclusions can be drawn. In the mean time, there will be plenty of opportunities to milk this research finding for humorous quips at late night talk shows.
Image credit: Co-culture of pre-adipocytes with mouse endothelial cells, via Wikimedia, Authors: Alexes Daquinag, Glauco Souza
Mitschke, M., Hoffmann, L., Gnad, T., Scholz, D., Kruithoff, K., Mayer, P., Haas, B., Sassmann, A., Pfeifer, A., & Kilic, A. (2013). Increased cGMP promotes healthy expansion and browning of white adipose tissue The FASEB Journal DOI: 10.1096/fj.12-221580