The dual role of asprosin in chronic fatty liver disease

Around 30% of the world’s population suffers from a chronic liver condition called metabolic dysfunction-associated steatotic liver disease, or MASLD, where excess fat accumulates in the organ and exceeds 5% of the organ’s total weight. Previously known as non-alcoholic fatty liver disease, MASLD is a subtype of hepatic steatosis or fatty liver disease that is not related to alcohol consumption and is the leading cause of liver-related mortality in humans.

Symptoms of MASLD often remain silent and develop slowly over many years before progressing into an inflammatory state known as metabolic dysfunction-associated steatohepatitis, or MASH. At this stage, the liver is damaged, leading to organ scarring, liver failure and even hepatocellular carcinoma, a type of liver cancer. These serious complications can ultimately be fatal. People with metabolic conditions like obesity, insulin resistance and type 2 diabetes are at a particularly high risk of developing this disease.

In a recent article published in the Journal of Lipid Research, Joshua Ayork Acevedo–Carabantes and a team of researchers at the Salvador Zubirán National Institute of Health Sciences and Nutrition uncovered the dual role of asprosin, a recently identified adipokine, a hormone secreted by adipose tissue, in MASLD. In the study, they treated primary cultured hepatocytes and diet‑induced obesity mouse models at different stages of obesity with asprosin and observed the hormone’s effect on lipid metabolism in the liver. At early stages, asprosin elevated the expression of mRNAs and proteins involved in fat breakdown and prevented fat accumulation in the liver, resulting in a protective effect and preventing disease progression. However, as obesity progressed, this protective effect was lost, and higher levels of the hormone indicated severe disease. To validate these results clinically, researchers measured serum asprosin levels in individuals who underwent FibroScan imaging, a diagnostic technique that uses ultrasound to determine liver fat accumulation and stiffness. They found that individuals with more advanced disease, evident from increased liver fat and stiffness, had elevated levels of asprosin compared to healthy individuals. 

This study shows that asprosin is protective at early stages of MASLD, but as the disease progresses, asprosin levels increase. As a result, increasing levels of asprosin can serve as a biomarker in healthcare settings to detect deteriorating liver health and disease progression in patients with MASLD.