Penn team shines a light on creating brown fat to fight diabetes

A team of investigators at the University of Pennsylvania has been making progress on the brown-fat front in the fight against obesity and diabetes.

University of Pennsylvania's Joseph Baur

Brown fat has been an intriguing, and frustrating, target for several years now. Researchers know that brown fat can accelerate fat burning. And now at Penn scientists say that they have been able to pin down a better understanding of the key pathway involved in "beiging" white fat cells into brown and turning it into a viable new approach to obesity as well as diabetes.

Joseph Baur, an assistant professor of physiology in the Perelman School of Medicine, focused on the role of the mTOR pathway. Contrary to earlier studies, he concluded that activating the mTORC1 protein complex--rather than inhibiting it--was necessary for cold-induced "beiging" of white fat, creating the cells needed to burn calories and control blood sugar and cholesterol.

The team tested this approach using the immunosuppressant rapamycin on mice, inducing insulin resistance by inhibiting both mTORC1 and mTORC2.

Actually getting a brown or beige fat drug into the clinic would be no small accomplishment. Third Rock tried and failed with Ember Therapeutics, satisfied that their approach would have to spend significant time and money on research before it could hope to see any product approval. Academics, though, continue to see real potential for new drugs that can thread this needle and improve the average person's "healthspan," improving health over an extended period.

"Our study highlights the complex interconnection between mTOR signaling and metabolism," said first author Cassie Tran, a postdoctoral fellow in the Baur lab. "It will be critical in moving forward to determine the specific targets downstream of mTOR that are causing the negative metabolic effects in order to create better drugs and one day drugs that might also extend healthspan. The discovery of a critical signaling pathway for beige-fat formation also suggests the opportunity to target this pathway to therapeutically increase the number of heat-producing cells in obese or diabetic patients."

- here's the release