Fatty liver disease, a condition where fat builds up in the liver, is linked to high-fat diets and obesity and is becoming a major global health issue. This condition raises the risk for various health problems. While most research has looked at how fat is processed in the liver itself, recent studies show that the gut also plays an important role in managing liver fat. Certain gut hormones, known as proglucagon-derived peptides (PGDPs), like glucagon, GLP-1, and GLP-2, help regulate fat processing in the liver. Although previous studies have shown that GLP-1 and GLP-2 are involved in liver fat buildup, their exact roles are still not completely understood.
A recent study by Associate Professor Yusuke Seino at Fujita Health University, published in Nutrients, investigates how PGDPs affect fat absorption and liver fat accumulation. The research team studied genetically modified mice lacking PGDPs (called GCGKO mice) to see how they responded to a high-fat diet for a week, revealing new ways to prevent fatty liver.
Key Findings
The study found that GCGKO mice, when fed a high-fat diet, had much lower levels of fat build-up in the liver compared to normal mice. Specifically, these mice showed reduced levels of free fatty acids (FFA) and triglycerides in the liver, along with lower body fat. This was due to a decrease in fat absorption in the intestines, even though the mice’s ability to burn fat in the liver was also reduced.
In addition, the research showed that GCGKO mice had lower levels of certain genes involved in fat breakdown, such as Pparα and Cd36, which help control fat uptake in the intestines. The reduced activity of these genes in the duodenum, the upper part of the small intestine, led to lower fat absorption and more cholesterol being excreted in feces. This suggests that the absence of PGDPs may help prevent fatty liver by reducing fat absorption in the intestines.
Gut Health and Fat Absorption
The study also observed changes in gut bacteria in GCGKO mice fed a high-fat diet, with increased levels of Parabacteroides and decreased Lactobacillus, bacteria known for supporting resistance to obesity. This finding suggests that both diet and hormones may influence gut health and overall metabolism.
Dr. Seino hopes that by studying how PGDPs regulate fat absorption in the gut, researchers can better understand the connection between diet, hormones, and gut bacteria, leading to diet recommendations that help prevent obesity and fatty liver disease.
Potential New Treatments
In the future, medicines that block GLP-2 and glucagon could help manage obesity and fatty liver by improving insulin sensitivity and fat metabolism. These findings open the door for new targeted treatments to help millions of people affected by fatty liver disease worldwide.
