Proteins that spur metabolism can be activated by cashew nut byproduct

One strategy to treat metabolic diseases such as diabetes and obesity is to target the molecular processes that regulate metabolism. Carolyn Cummins, associate professor at the Leslie Dan Faculty of Pharmacy, and collaborators from the University of Brasilia in Brazil have demonstrated that a byproduct of the cashew nut shell can do just that.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors – proteins that bind to DNA and alter gene expression – that regulate a number of important cell processes. For example, activation of PPARs, whether through medication or dietary fatty acids, triggers liver cells to increase fatty acid uptake and use, and muscle cells to increase glucose uptake, among other activities.

Cummins’ team studies nuclear receptors, including PPARs, and their roles in the development of diabetes, obesity and other metabolic diseases, as well as the potential of targeting PPARs with drugs to treat these diseases. Several years ago, Cummins and collaborators in Brazil identified that a molecule called LDT409, which is found in cashew nut shells and is a byproduct of the nut industry, could potentially activate PPARs.

In 2024, they published the results of a study examining LDT409 in mice fed high-fat diets. The study demonstrated that LDT409 activated two forms of PPAR and reversed obesity in their mouse models. By activating PPARs, the molecule results in increased energy expenditure, decreased food intake, and increased fat utilization and excretion in mouse models.

Listen to Associate Professor Carolyn Cummins discuss drug discovery on the I'm Pharmacy Podcast.

“This work shows that the unique profile of the molecule in activating two forms of PPAR gives it advantages for treating metabolic disease over traditional activators of these receptors,” says Cummins.

“Taken together, our data support the idea that LDT409 is a promising candidate drug to treat both obesity and diabetes. And because LDT409 is synthesized from a waste product of the cashew industry, it would serve as an economical starting material for a potential drug.”