A team of scientists has demonstrated that a Western diet rich in fat and sugar may cause hepatic inflammation, especially in males, and is likely to progress into advanced liver diseases such as cancer if left untreated.
The study, led by Yu-Jui Yvonne Wan of UC Davis Health, assumes significance as it links diet to changes in the gut microbiota as well as bile acid profile. This opens the possibility that probiotics and bile acid receptor agonists may be useful for the prevention of hepatic inflammation.
“We know the transition from steatosis, or fatty liver, to steatohepatitis (inflammation in the fatty liver) plays a crucial role in liver injury and carcinogenesis. Because the liver receives 70% of its blood supply from the intestine, it is important to understand how the gut contributes to liver disease development,” said Wan.
Wan’s team used a FXR-deficient mouse model to demonstrate the role of diet and inflammation in the development of liver diseases, including cancer because patients with cirrhosis or liver cancer also have low FXR levels.
Earlier studies have already shown that FXR-deficient mice spontaneously develop steatohepatitis and liver tumours even when they are fed a normal rodent diet. In this study, wild-type and FXR-deficient mice were fed either a Western diet or a matching control diet for 10 months.
They found similarities between Western diet intake and FXR deficiency. For instance, both Western diet-fed wild-type mice and control diet-fed FXR KO mice developed steatosis, which also was more severe in males than females.
Interestingly, however, only the FXR-deficient male mice had massive lymphocyte and neutrophil infiltration in the liver, and only Western diet-fed male FXR KO mice had fatty adenomas.
“These studies show that a Western diet intake and FXR inactivation also increased hepatic inflammatory signaling, with a combined enhanced effect,” Dr Wan said. “Introducing antibiotics to reduce inflammation also had different effects based on the diets the mice received,” she added.
The study was recently published in The American Journal of Pathology.