Discoveries

GLP-1s are building a reputation as “wonder drugs.” First characterized for their ability to improve insulin release and treat diabetes, the drugs were later found to promote weight loss and improve cardiovascular health. In addition to those bonus benefits, GLP-1 drugs can improve pancreatic beta cell health. But how, exactly, are they doing that?

In the lab of Marc Montminy, MD, PhD, scientists are burrowing into the mechanistic details behind how GLP-1 drugs promote viability and stress resistance in pancreatic beta cells. Since cellular performance adaptations arise from gene expression changes, the team screened for regulatory proteins that can switch on gene programs responsible for the beneficial effects of prolonged use of GLP-1 therapeutics. They identified a protein called Med14—part of a larger protein complex called Mediator—that enables the GLP-1-dependent changes in gene expression that lead to pancreatic health benefits.

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Metabolic dysfunction-associated steatotic liver disease (MASLD) is among the most common chronic liver diseases and, when untreated, can progress to cancer, cardiovascular disease, and diabetes. A new study led by Ronald Evans, PhD, found that production of the protein FGF1 in the liver varies throughout the day to regulate the timing of fat release from the liver into the bloodstream, acting as a circadian pacemaker for liver fat metabolism. 

This liver clock ensures fat enters the bloodstream on a precise daily schedule and prevents fat accumulation seen in MASLD. The findings may also help explain why circadian disruption, from shift work to chronic sleep loss, has been linked to metabolic disease. Each mechanistic step uncovered brings scientists closer to therapies grounded not just in symptom management, but also in the fundamental biology of how the body regulates fat.

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Some of your most important life partners are the mitochondria that power all your cells. You and these little cellular powerhouses are in a 1.5-billion-year-old evolutionary relationship—but mitochondria brought some baggage. Mitochondria brought their own DNA with them when they joined with our bigger, more complex cells so long ago, and today, that mitochondrial DNA influences human health.

Ronald Evans, PhD, is asking what those influences are, and the latest study from his lab unveils a new biological platform for studying mitochondrial DNA in physiology, adaptation, disease mechanisms, and therapeutic development. They have already used the platform to generate a library of 155 mitochondrial DNA mutant cell lines and to reveal correlations between mouse development and mitochondrial function. The platform, library, and findings will accelerate therapeutic development for mitochondrial disorders and help scientists treat mitochondrial dysfunction in other diseases and conditions, such as cancer and aging. 

“The majority of human diseases come with or cause mitochondrial dysfunction. Progress in this field has been limited, but this new platform is going to fuel so much important research that points to therapeutic approaches to combat mitochondrial diseases, as well as diseases or conditions associated with mitochondrial dysfunction like cancer or aging.”

Ronald Evans 

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