SC Connecticut News

Researchers are intensifying their efforts to find solutions for fatty liver disease, also known as metabolic dysfunction-associated steatotic liver disease (MASLD). This condition affects nearly 40% of adults in the U.S. and can lead to severe health issues, including inflammation, fibrosis, permanent liver damage, or even liver cancer.

A recent study by Yale School of Medicine (YSM), published on August 27 in the journal Cell Metabolism, has made significant findings regarding MASLD. According to Gerald Shulman, MD, PhD, senior author and George R. Cowgill Professor of Medicine (Endocrinology) at YSM, the research indicates that individuals with MASLD burn fat in their livers at the same rate as those without the disease. The study's findings also highlight that increasing blood levels of glucagon—a glucose-related hormone—stimulates liver metabolism in both healthy individuals and those with fatty liver disease.

Shulman noted the importance of these findings: "It’s clear that we need other agents," he said, referring to therapies aimed at enhancing mitochondrial fat oxidation in the liver. Existing treatments like resmetirom do not work for all patients.

The researchers used a novel technique called positional isotopomer NMR tracer analysis (PINTA) to examine liver metabolism in real-time within the body. This method allowed them to trace labeled substrates' metabolism and quantify rates of mitochondrial oxidation and gluconeogenesis. The study involved 12 healthy volunteers compared with 13 volunteers with MASLD and another 13 with a less severe form known as metabolic dysfunction-associated steatotic liver (MASL).

Their results showed similar rates of mitochondrial oxidation across all groups but revealed that glucagon infusions significantly increased hepatic mitochondrial fat oxidation by 50 to 75%. "This suggests that increasing glucagon will have additive beneficial effects to reduce liver fat," Shulman explained.

Medications that boost glucagon levels could potentially treat fatty liver by enhancing energy expenditure. Current GLP-1 agonist drugs such as semaglutide (Ozempic) already alleviate excess liver fat through weight loss and reduced energy intake. Experimental combination drugs pairing GLP-1 agonists with compounds raising glucagon levels have shown promise in treating fatty liver disease effectively.

Shulman and his team plan further research using their method to test various metabolism-related drugs on liver metabolism over extended periods to determine if the benefits of glucagon persist long-term.