Study Links Cellular Receptor GPR75 to the Progression of Liver Disease
Findings by New York Medical College Researchers Could Offer a New Path to Treating Liver Disease
Liver disease—particularly chronic forms like metabolic dysfunction-associated liver disease (MASLD) and cirrhosis—represents a major global health challenge, responsible for millions of deaths annually. Yet despite its severity and rising prevalence, current treatments mainly manage complications rather than stop or reverse the disease itself. A new study by researchers at New York Medical College (NYMC), published in Frontiers, offers hope for changing that, potentially paving the way for more effective therapies that improve outcomes for people with liver disease.
While it was long known by scientists that 20-hydroxyeicosatetraenoic acid (20-HETE)—a pro-inflammatory lipid—can impair vascular function, raise blood pressure, and become elevated in response to high-fat diets—increasing the risk of both cardiovascular and metabolic disease—pinpointing the cell proteins that reacted to the signal of 20-HETE were unclear. That changed in 2013 when research by the labs of Michal Laniado Schwartzman, Ph.D., the Alumni Endowed Chair of Biomedical Sciences and professor and chair of pharmacology, and Victor Garcia, Ph.D.’15, associate professor of pharmacology, at NYMC, identified the orphan G protein-coupled receptor GPR75 as the likely candidate. Subsequent research has linked GPR75 to obesity, diabetes, and, more recently, liver disease.
“Our current study is the first to look closely at how 20-HETE, CYP4A11 (a major enzyme that produces 20-HETE) and the receptor GPR75 interact as liver disease progresses in human patients,” says Dr. Garcia, who collaborated with researchers at Northeast Ohio Medical University and the National Institute on Alcohol Abuse and Alcoholism, on the study. “While a deficiency in GPR75 can protect against obesity and liver fat buildup, its expression across MASLD and hepatocellular carcinoma was not clearly understood. This work fills that gap by showing how GPR75 is regulated across different stages of liver disease, and most importantly, underscores the potential of GPR75 in developing therapies to prevent and reverse not just obesity but liver damage and disease as well.”
According to Dr. Garcia, these findings could eventually reshape how liver disease is treated. “Understanding the 20-HETE/GPR75 pathway opens the door to new medications that don’t just treat symptoms but actually slow, stop, or even reverse the progression of liver disease to more severe stages like cirrhosis or liver cancer. Interestingly, GPR75 also plays a role in various cancers, including prostate cancer. Tracking levels of 20-HETE and GPR75 could lead to earlier and more accurate diagnosis. Our findings also highlight why it’s so important to have tests that can help catch issues early, even before you feel sick, because these harmful signals may already be at work before symptoms start.”
