Scientists Identify Link Between Excess Dietary Salt and 'Lean MASH'

High salt intake may contribute to a severe form of fatty liver disease in people with normal body weight, according to a mouse study published in Molecular Metabolism.

Researchers from Duke-NUS Medical School developed a diet-induced mouse model of lean metabolic dysfunction-associated steatohepatitis, or lean MASH. This condition can occur in people who do not have obesity and is characterised by liver inflammation and scarring.

The researchers found that excess dietary salt changed how the liver processed fat. Although the diet increased fat breakdown, it also activated immune cells and inflammatory pathways in the liver. This combination produced severe inflammation and fibrosis despite relatively low levels of liver fat.

The findings may help explain why some people with a normal body mass index develop serious liver disease. Lean MASH is becoming increasingly recognised, particularly among Asian populations, but its environmental triggers and biological mechanisms remain poorly understood.

MASH is a progressive form of fatty liver disease that can cause persistent inflammation and scarring. In some patients, it can eventually lead to cirrhosis, liver failure and liver cancer. Cardiovascular disease is also a major cause of death among people with MASH.

The researchers said the findings suggest lean MASH may not simply be the same disease seen in people with obesity. Different biological pathways may contribute to liver injury, which could mean that treatments developed mainly for obesity-associated MASH may not work equally well in lean patients.

However, the findings are based on a mouse model and cannot establish that high salt intake causes lean MASH in humans. Human studies are needed to determine whether the salt-related pathway is relevant to patients.

Further studies could help determine whether patients may benefit from more personalised approaches to diagnosis and treatment.

REFERENCE: Luo, S., et al. (2026). High salt supplementation of a MASH-inducing diet causes lean MASH phenotype with increased hepatic urea cycle activity and EIF5A hypusination. Molecular Metabolism. DOI: 10.1016/j.molmet.2026.102417.