Scientists may be on the verge of an effective new treatment for diabetes and obesity, after designing a drug that can be injected directly into potentially harmful white fat and transform it into “good” brown fat.
White fat, or white adipose tissue, is a form of body fat that stores calories and accumulates as an energy reserve. It also provides insulation and helps to protect body tissue against injury by acting as a cushion.
However, consuming too many calories or not getting enough exercise can lead to an excess buildup of white fat. This may lead to obesity and associated health problems, such as type 2 diabetes and heart disease, particularly when white fat accumulates around the abdominal area.
Brown fat, or brown adipose tissue, is often referred to as the “good” body fat, as it burns calories to generate heat. As such, researchers have been searching for ways to increase brown fat in the body and reduce white fat, as a means of treating obesity and related conditions.
In previous research, Meng Deng – an assistant professor of agricultural and biological engineering, biomedical engineering, and materials engineering at Purdue University in West Lafayette, IN – and colleagues found that inhibiting “Notch signaling” in white fat can convert it into brown fat.
In detail, the team found that blocking the activity of a gene called Notch1 in white fat cells increases the expression of uncoupling protein 1 (Ucp1) – which is a protein that promotes fat burning – and leads to the browning of white fat.
Their latest study builds on this finding; the team has discovered a way to deliver a Notch-signaling inhibitor directly to white fat and turn it into brown fat.
Prof. Deng and colleagues recently reported their results in the journal Molecular Therapy.
The Notch-signaling inhibitor used in the study is a chemical compound called dibenzazepine, which is used as an anticonvulsant.
In order to deliver this drug to white fat cells directly, the researchers inserted it into nanoparticles comprised of PLGA, which is a polymer approved by the United States Food and Drug Administration (FDA).
On injecting the nanoparticle-drug combination into the white fat of mice, the researchers found that the nanoparticles were easily taken in by white fat cells.
“The particle was actually picked up by the cell. It’s like it’s being eaten by the cells,” says study co-author Shihuan Kuang, a professor of animal sciences at Purdue. “This limits the particle from going anywhere else.”
“Once those engineered particles are inside the fat cells, they can slowly release the drug in the cells, potentially limiting the off-target interactions in other tissue in the body and reducing the frequency of dosing,” adds Prof. Deng.
Importantly, the researchers found that the drug effectively inhibited Notch-signaling in the rodents, which converted potentially harmful white fat into calorie-burning brown fat.
Additionally, they found that weekly injections of the drug to a specific area of white fat improved insulin sensitivity and glucose tolerance in mice with diet-induced obesity.
Overall, the team believes that their results may pave the way for new therapies that can target specific areas of fat and help to treat obesity, which currently affects more than a third of U.S. adults.
“Our studies not only substantiate that the local browning induced by the Notch inhibition in WAT [white adipose tissue] improved energy homeostasis, but also offer new avenues to develop a potential therapeutic strategy for [the] clinical treatment of obesity and its associated metabolic syndrome.”