Gut Hormones’ Role in Fatty Liver Disease Prevention Explored
Updated June 19, 2025
Fatty liver disease, marked by excessive fat accumulation in the liver, is an increasing health crisis worldwide. Researchers at Fujita Health University investigated the role gut hormones play in this condition, specifically how they affect fat buildup in the liver.
Associate Professor Yusuke Seino led the study, which was published in Nutrients.The research team, including Koki Nishida, Atsushi Suzuki, Yoshiki Hirooka, and Yoshikata Hayashi, used genetically modified mice lacking proglucagon-derived peptides (PGDPs) too examine the impact of a high-fat diet on liver fat accumulation and the role of these peptides.
Seino noted that mice lacking PGDPs showed a significantly lower increase in liver free fatty acids and triglyceride levels when fed a high-fat diet for one week. this was linked to decreased lipid absorption in the intestinal tract, despite a reduced fat-burning capacity in the liver.
The study also revealed lower expression levels of genes involved in fatty acid oxidation in the PGDP-deficient mice. Specifically, Pparα and Cd36 mRNA levels were reduced in the duodenum, correlating with decreased intestinal fat uptake and increased fecal cholesterol content. This suggests that the absence of PGDPs prevents diet-induced fatty liver by reducing intestinal fat absorption, highlighting the role of gut hormones.
Researchers found that the primary factor preventing fat accumulation was reduced fat absorption from the intestines, even with lower fat-burning activity in the liver. Mice lacking PGDPs also exhibited lower plasma triglyceride levels, further confirming reduced lipid absorption.
The study also highlighted the relationship between diet, hormonal responses, and gut bacteria. Mice on a high-fat diet lacking PGDPs showed changes in gut bacteria, with an increase in Parabacteroides and a decrease in Lactobacillus, both associated with obesity resistance. These shifts suggest that dietary and hormonal interventions could enhance gut health and metabolic function, further emphasizing the role of diet.
“If we can examine in more detail how PGDPs specifically regulate lipid absorption in the gut, we hope to clarify the relationship between diet, hormones, and intestinal bacteria sufficiently to recommend a diet that is less conducive to obesity and fatty liver disease,” Seino said.
What’s next
Seino suggests that oral dual antagonists of GLP-2 and glucagon could be potential therapies for obesity and fatty liver, given their roles in insulin sensitivity and lipid metabolism. These findings could lead to targeted therapies to combat fatty liver disease.
