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A groundbreaking study from Japan has revealed the vital role gut hormones play in preventing dietary-induced fatty liver disease, a condition increasingly prevalent in today’s world due to high-fat diets and rising obesity rates. The research, conducted by scientists from Fujita Health University, focused on the role of intestinal absorption in protecting against fat accumulation in the liver, which poses significant risks for metabolic disorders.
Fatty liver disease, characterized by excessive fat buildup in the liver, is linked to an increased risk of conditions like diabetes, cardiovascular disease, and liver cirrhosis. While most research on fatty liver disease has historically centered around the liver’s own fat metabolism, the new study shifts the focus to the gut, revealing that hormones regulating fat absorption may be key to managing this condition.
In the study, published in the journal Nutrients, researchers examined the role of proglucagon-derived peptides (PGDPs)—hormones including glucagon, GLP-1, and GLP-2—known for their role in lipid metabolism in the liver. Using lab-generated mice with inactivated PGDP genes (GCGKO mice), they compared the animals’ response to a high-fat diet (HFD) over the course of seven days with that of control mice.
Associate Professor Yusuke Seino, one of the study’s lead authors, explained that despite both groups being subjected to the same high-fat diet, the GCGKO mice displayed significantly lower levels of hepatic free fatty acids (FFAs) and triglycerides, alongside reduced adipose tissue weight compared to their counterparts. These findings suggest that the absence of PGDPs led to a decrease in fat absorption from the intestines, even though the liver’s fat-burning capacity was diminished.
“The study highlights the importance of gut hormones in regulating fat absorption and preventing liver fat buildup,” Seino said. “This opens up the possibility of using dual antagonists of GLP-2 and glucagon as therapeutic options for managing obesity and fatty liver.”
Additionally, the researchers observed shifts in the gut microbiota of the mice on high-fat diets. Specifically, there was an increase in Parabacteroides and a decrease in Lactobacillus—bacteria previously associated with resistance to obesity. These findings point to the complex interplay between diet, hormonal responses, and gut bacteria in the development of fatty liver disease.
This study suggests that therapies targeting gut hormones could potentially offer new strategies for treating not only fatty liver disease but also associated metabolic disorders like obesity and insulin resistance. With fatty liver disease becoming a major global health concern, these findings provide a promising avenue for future research and therapeutic development.
By addressing the gut’s role in lipid metabolism, this study reinforces the need to look beyond the liver itself in combating fatty liver disease and related conditions.
