Converting Fat Cells into Calorie Burners in the Corvera Lab

A study by the Corvera laboratory investigated a protein called UCP1 (uncoupling protein 1) found in brown or beige adipocytes.  UCP1 helps those fat cells to generate heat, burn calories, and control the internal temperature of critical organs.

“My lab has developed novel approaches to study human adipose tissue so we can better understand its composition, molecular mechanisms, and functions,” said Silvia Corvera, MD, Professor, Program in Molecular Medicine, Endowed Chair in Diabetes Research, and Director, Clinical Translational Research Pathway, T.H. Chan School of Medicine.

Scientists have long known that UCP1 production increases when fat cells are exposed to certain hormones that raise levels of cAMP (cyclic Adenosine Monophosphate), which acts as a messenger molecule inside our cells. It helps to carry signals that can trigger various changes in cell behavior.  This process was thought to be the main way UCP1 production is activated.

The Corvera lab study, published in Molecular Metabolism December 2024, identified another way to boost UCP1 production, involving a protein called PPARγ (Peroxisome Proliferator-Activated Receptor gamma).  PPARγ acts like a switch in our cells to change how our bodies use energy and store fat.  When turned on, it can rapidly increase UCP1 production in fat cells.  This new pathway can increase UCP1 production quickly, without waiting for new fat cells to develop. 

“Understanding this pathway could lead to new ways to increase heat production in fat cells, which might help with weight loss or metabolic health,” said Dr. Corvera.

Their experiments found that Rosiglitazone, an FDA approved type 2 diabetes drug that activates PPARγ, also increased UCP1 production in the fat cells.  Forskolin, a plant-based product used as a weight loss supplement, increases cAMP levels.  However, when the two were combined and used together, they had an even stronger effect on UCP1 production than either one alone.

“Our study showed that both the traditional cAMP pathway and this new PPARγ pathway can work together, leading to even greater UCP1 production,” said Dr. Corvera. “It suggests that these drugs can make existing fat cells produce more UCP1, rather than creating new beige fat cells,” said Dr. Corvera.

Learning how to make brown fat burn more calories has to potential to help people maintain a healthy weight.  It's like turning up the heat in fat cells that are already there, instead of building new heating systems.  Combining or modifying these existing drugs could lead to new treatments for obesity, diabetes, and related health problems.  

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