High-Salt Diets May Drive Severe Fatty Liver Disease in Lean Individuals, Study Finds
Fatty liver disease is widely recognized as a condition heavily tied to obesity. However, an increasing number of individuals who maintain a normal body mass index are developing a severe and progressive form of the illness. Researchers at Duke-NUS Medical School have now identified a distinct biological mechanism involving dietary salt that may help explain why this occurs in people who are not overweight.
The condition, known as metabolic dysfunction-associated steatohepatitis (MASH), is a serious and progressive liver disease characterized by persistent inflammation and tissue scarring. If left unmanaged, MASH can eventually advance to life-threatening complications such as cirrhosis, liver failure, and liver cell cancer. While obesity remains a primary risk factor, MASH prevalence is climbing globally—particularly in Westernized Asian populations—where up to 40% of cases occur in people with normal body weights, a phenomenon frequently referred to as lean MASH.
To better understand the biological triggers behind this condition, a collaborative team of scientists including researchers from Duke-NUS, the National Heart Centre Singapore, the Duke University School of Medicine, and University College London developed a specialized diet-induced mouse model. The findings of their investigation were published in the journal Molecular Metabolism.
Uncovering a Distinct Biological Pathway
Historically, studying lean MASH has presented a major challenge for the scientific community due to a lack of accurate laboratory models that mirror the human condition. The newly developed model successfully replicates key characteristics of lean MASH in humans, featuring relatively low levels of accumulated liver fat alongside severe liver inflammation and tissue scarring. This reflects a dangerous clinical pattern where patients may show less overall fat in the liver yet face a significantly higher risk of severe medical complications.
According to the study, consuming excess dietary salt alters how the liver processes and handles fat. Instead of simply causing fat to build up, high salt intake simultaneously increases fat breakdown while activating specific immune cells that provoke aggressive inflammation within the liver tissue.
Dr. Zhou Jin, lead author of the study and a principal research scientist at the Duke-NUS Cardiovascular & Metabolic Disorders Signature Research Programme, emphasized that these findings challenge traditional assumptions about the disease. Dr. Jin noted that lean MASH appears to be fundamentally different from obesity-associated MASH rather than simply being the same condition in a thinner person. While traditional MASH is closely tied to excess fat storage, high dietary salt can alter liver metabolism and trigger inflammatory pathways independently of obesity. The researchers caution that this distinction is crucial because therapies designed specifically to target obesity-driven MASH may fail to address the underlying drivers of disease in lean patients.
Implications Beyond Liver Health
Because cardiovascular disease stands out as a primary cause of death among patients suffering from MASH, establishing a reliable preclinical model offers broad implications for overall health. Professor Derek John Hausenloy, a co-author of the study from the Duke-NUS Cardiovascular & Metabolic Disorders Signature Research Programme, pointed out that the model allows researchers to examine lean MASH as a whole-body condition rather than an isolated liver ailment. Investigators can now explore whether the identical mechanisms driving liver injury in lean patients also exert harmful effects on cardiovascular function.
Professor Lok Shee-Mei, vice dean of the Office of Research at Duke-NUS, underscored that the research highlights the need for personalized medicine in hepatology. By uncovering a unique disease mechanism and establishing a functional preclinical model, the research team has laid a solid groundwork for developing diagnostic tools and therapies tailored to individual patient biology.
Moving forward, the research team plans to utilize this new model to identify early diagnostic biomarkers for lean MASH. They also aim to test therapeutic compounds capable of selectively blocking the salt-driven inflammatory pathways identified in the study, which could ultimately help clinicians detect the disease earlier and select the most effective treatments.
Source: Medical Xpress
