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.
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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.