Researchers from the Columbia University Medical Center (CUMC) and the University of North Carolina have managed to devise a microneedle skin patch that could locally treat both obesity and diabetes. As of now it has been used to treat mice in the laboratory and shown promising results.
The skin patch that has been developed has been able to convert the energy-storing white fat in the body into energy –burning brown fat. This conversion along with a rise in the overall metabolism of the animal manages to burn off more fat and treat obesity. The patch was selectively applied over areas where fat is deposited for examples at the animal equivalent of the “love handles” in humans. In those areas, it successfully removed the excess fat deposits. This is hailed as the next big thing in treatment of obesity, type 2 diabetes and other metabolic disorders. These findings were published online in a study entitled, “Locally-Induced Adipose Tissue Browning by Microneedle Patch for Obesity Treatment.” in ACS Nano.
White and Brown Fat
There are two types of fat in the body – white and brown. The white fat is the one that stores the energy and gives rise to layers of the fat that gets accumulated in certain parts of the body including the central regions. It contains large droplets of triglycerides and these are the source of energy when the body is fasting. The other type of fat is the brown fat. In this the fat droplets are much smaller. They also have cellular powerhouses called the mitochondria. These mitochondria break down the brown fat to produce energy more readily compared to white fat. Newborn babies have more brown fat than white and this helps protect them from the surrounding cold temperatures. As a person reaches adulthood, much of this brown fat is lost.
One of the significant understandings of these body fat types is an attempt to convert this white fat to brown so that it can be readily burnt off. This happens naturally when a person is exposed to cold temperatures but otherwise was deemed difficult. This conversion was thought to be the treatment for diabetes and obesity.
Li Qiang, assistant professor of pathology & cell biology at Columbia and part of the study explained that there are pills and injections that can promote more brown fat than white in the body but these drugs can affect the whole body leading to side effects such as increased propensity for weight gain, stomach ailments and fractures of the bones. This new method of using a skin patch affects only the desired area and does not affect the rest of the body.
For this study the team of researchers first developed the drugs to be encapsulated in nanoparticles measuring 250 nanometers (nm) in diameter. This size is comparable to a human hair thickness that is 100,000 nm. As a next step these particles are set onto a centimeter-square skin patch that has microneedles or microscopic needles. When put overt the skin, these needles penetrate the skin without causing pain and slowly release the medication into the tissues just beneath the skin.
Zhen Gu, PhD, associate professor of joint biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University explained that the nanoparticles are made in such as way that they would carry the drug to the site of action and after releasing the drug in a steady manner gradually collapse. The drug stays only at the tissue released in this manner. The drugs used in the nanoparticles are one of the two agents that can convert white to brown fat - rosiglitazone (Avandia) or CL316243, a beta receptor agonist that can convert white to brown fat.
For this study every mouse was given two patches – one with the drug carrying nanoparticles and the other with nanoparticles that did not have the drugs. The patches were attached to both sides of the lower belly of the mice. The patches were changed every three days for a total of four weeks. Some of the mice served as a control group where they were given two patches with empty nanoparticles.
Results revealed that the mice that were given patches with either of the two drugs showed a 20 percent reduction in the fat deposits over the site where the drug was applied compared to those regions where empty patches were applied. The blood sugar of these animals who were treated with the drugs were also lower. If the treated mice were not fat (lean mice), when either of the two drugs were applied, the animals’ oxygen consumption was raised by around 20 percent. This is an indicator that their metabolism rose. Genes were tested on the treated sides and it was seen that those treated sites now had more genes related to brown fat compared to the other sites.
Dr. Qiang noted that this was probably a more “noninvasive” method that could reduce pockets of fat compared to liposuction. He added that these patches would not be just for cosmetic use but would be a safer alternative to treating metabolic diseases such as obesity and diabetes. The next step would be to try the patches on humans and check for their efficacy and safety in clinical trials.
The study was supported by grants from the North Carolina Translational and Clinical Sciences Institute and the National Institutes of Health.