GLP-1 drugs have direct beneficial effects on the liver, independent of their benefits for obesity, researchers studying the medicines in mice with fatty liver disease have found.

Scientists had believed that liver cells do not have the surface proteins, or receptors, targeted by these drugs, suggesting that they likely had no direct route to the liver.

In experiments with mice with fatty liver ‌disease, researchers found that certain liver cells do carry receptors for semaglutide, the GLP-1 drug sold by Novo Nordisk as ​Ozempic for diabetes and Wegovy for weight loss.

The cells, called liver sinusoidal endothelial cells, or LSECs, account for only about 3% of all liver cells. They line tiny blood vessels in the liver and ⁠are studded with pores that allow them to filter substances passing between the liver and the bloodstream. Semaglutide shifts gene activity ​in LSECs, prompting them to release molecules that help reduce inflammation throughout the liver, the researchers reported on Tuesday in Cell Metabolism.

“We’ve ⁠seen in clinical trials that patients (taking GLP-1 drugs) who lose very little weight see the same reductions in liver inflammation, scarring and enzyme levels as those who lose a great deal of weight. Now we know why,” study leader Dr. Daniel Drucker of Sinai Health in Toronto said in a statement.

“We're not ‌saying weight loss isn't important because many things improve when patients lose weight,” he added.

“But we now know ​that weight shouldn't be ‌the only measure of success, because GLP-1 medicines will improve liver health whether or not the patient loses weight.”

RESEARCHERS DISCOVER HOW OBESITY IMPAIRS VACCINE RESPONSE

A new study sheds light on ‌why traditional vaccines that rely on high antibody production tend to be less effective in people with obesity.

For the study, mice with obesity were vaccinated against a common bacteria called Pseudomonas aeruginosa, a leading cause of severe pneumonia for people with obesity.

The ⁠researchers discovered that the decreased quality and longevity of ‌antibody responses to the vaccine was due ⁠to defects in so-called germinal centers in the lymph nodes and spleen, where specialized immune cells called B cells produce antibodies and learn to recognize and remember germs.

Although ⁠the antibody ⁠response was impaired, the vaccine did generate a strong response from immune cells that live permanently in the lungs and do not circulate through the bloodstream, known as tissue-resident memory ‌T cells.

In response to the P. aeruginosa vaccine, resident memory T cells provided early, critical protection against infection, which suggests they could be helping to compensate for antibody deficiencies, the researchers said. Emerging antibiotic resistance increasingly makes the infection difficult to treat, highlighting the need for effective vaccines, according ‌to a ​report of the study in the Journal ‌of Immunology.

“We hope these findings shift the focus of vaccine design and lead to more effective, tailored vaccines for the millions of people living with obesity who are at higher risk for severe respiratory infections,” study leader Wendy ​Picking of the University of Missouri said in a statement.

“We should intentionally design vaccines that prioritize tissue-resident immunity, ensuring protection directly where pathogens like Pseudomonas enter the body,” Picking said.