A study led by researchers from the Texas A&M University System and Central Texas Veterans Health Care System, or CTVHCS, shows how a protein known as STING could be a therapeutic target for non-alcoholic fatty liver disease or NAFLD.

The study, "Expression of STING Is Increased in Liver Tissues from Patients with NAFLD and Promotes Macrophage-mediated Hepatic Inflammation and Fibrosis in Mice," was recently published online in the journal Gastroenterology.

The study included participation from Baylor Scott and White Health in Temple and the Veterinary Medical Teaching Hospital of Texas A&M University in College Station.

"The study showed nutrition intervention that would target STING to suppress inflammation could be a novel approach for prevention of non-alcoholic fatty liver disease," said Dr. Chaodong Wu, a Texas A&M AgriLife Research scientist in the nutrition and food science department at Texas A&M in College Station.

Wu said transmembrane protein 173, also called TMEM173 or STING, functions as a major regulator of the innate immune response to viral and bacterial infections using macrophage signaling. Macrophages are cells of the immune system that detect, surround and destroy bacteria and other harmful organisms.

Macrophages function

"However, if there is nutrition stress, macrophages function differentially from those responding to infection, contributing to hepatic steatosis, which is an unusual buildup of fat in the liver and non-alcoholic fatty liver disease," he explained.

Wu said the purpose of the study was to discover if STING would also regulate diet-induced activity in hepatic steatosis, inflammation and liver fibrosis. "To test this hypothesis, we used mice in which we disrupted the STING gene, mice without disruption of this gene and mice with STING disruption only in myeloid cells," he explained.

"The mice were fed a standard chow diet, a high-fat diet of 60% fat calories or a methionine- and choline-deficient, or MCD, diet," Wu explained.

Study results showed non-parenchymal liver cells those who interact with hepatocytes and with each other by soluble mediators and direct cell-to-cell contact from patients with the non-alcoholic fatty liver disease had higher levels of STING than liver tissues from patients without the disease.

"STING mice and mice with STING disruption only in myeloid cells developed less severe hepatic steatosis, inflammation and/or fibrosis following a high-fat or MCD diet than control mice," said Dr. Gianfranco Alpini, distinguished professor in the department of medical physiology at Texas A&M College of Medicine in Temple and research career scientist at the CTVHCS.

"Biochemical markers of inflammation were significantly lower in liver tissues from STING mice as compared to control mice after being fed these two types of diet," said Alpini.

Alpini said transplantation of bone marrow cells from control mice to STING mice further confirmed this response by restoring the severity of steatosis and inflammation following a high-fat diet.