Hepatic Fat

Hepatic Fat

Hepatic fat, also called intrahepatic triglyceride content, is the build-up of fat droplets inside liver cells. A healthy liver contains less than 5% fat by weight. Above that threshold, the condition is called hepatic steatosis, the defining feature of metabolic dysfunction-associated steatotic liver disease (MASLD, formerly non-alcoholic fatty liver disease or NAFLD). Liver fat builds up when more fat comes in (from free fatty acids in the blood, fat made in the liver and diet) than goes out (through fat burning and release of very-low-density lipoprotein). MRI-derived proton density fat fraction (MRI-PDFF) has become the gold-standard non-invasive way to measure liver fat. It is sensitive and repeatable enough to track changes in clinical trials.

High liver fat is closely tied to insulin resistance, as both a result and a cause of metabolic problems. Fat inside liver cells blunts insulin signaling, so the liver keeps releasing glucose when it should stop, which raises blood sugar. Fatty liver can also progress to steatohepatitis (MASH), with liver cell injury, inflammation and scarring (fibrosis), and eventually to cirrhosis and liver cancer. MASLD is estimated to affect 25-30% of adults worldwide and is much more common in people with obesity and type 2 diabetes.

Clinical Relevance to Retatrutide

Retatrutide has cut liver fat sharply in clinical studies. Its glucagon receptor activity matters most here: glucagon signaling in the liver directly increases fat burning and reduces new fat production, hitting the root causes of liver fat build-up. In phase 2 trials, people on retatrutide had large drops in liver fat measured by MRI-PDFF, and many reached normal levels (below the 5% threshold). These findings have drawn strong interest in retatrutide as a possible treatment for MASLD and MASH, and dedicated studies of its effects on liver tissue are underway.