Effect of pemafibrate in reducing intestinal long-chain fatty acid absorption and hepatic fibrosis in metabolic dysfunction-associated steatohepatitis rats

Abstract Background Pemafibrate helps regulate fatty acid dynamics in the liver, potentially preventing metabolic dysfunction-associated steatohepatitis (MASH). However, its effect on intestinal long-chain fatty acid (LCFA) metabolism in MASH remains unclear. Thus, we aimed to examine the influence...

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Main Authors: Masaya Okada, Masakazu Hanayama, Yasunori Yamamoto, Teruki Miyake, Osamu Yoshida, Eiji Takeshita, Yoshio Ikeda, Yoichi Hiasa
Format: Article
Language:English
Published: BMC 2025-05-01
Series:BMC Gastroenterology
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Online Access:https://doi.org/10.1186/s12876-025-03967-z
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Summary:Abstract Background Pemafibrate helps regulate fatty acid dynamics in the liver, potentially preventing metabolic dysfunction-associated steatohepatitis (MASH). However, its effect on intestinal long-chain fatty acid (LCFA) metabolism in MASH remains unclear. Thus, we aimed to examine the influence of pemafibrate on intestinal LCFA metabolism and hepatic fibrosis in a MASH rat model. Methods Sprague–Dawley rats were fed a high-fat and high-cholesterol diet to induce MASH and then divided into pemafibrate-treated (pemafibrate (+)) and untreated (pemafibrate (-)) groups. Triglyceride deposition in the small intestine and fibrosis, along with α-smooth muscle actin level in the liver, were evaluated. Furthermore, the mRNA expression levels of genes associated with lipid metabolism in the small intestine and markers of fibrosis and hepatic stellate cells activation in the liver were measured. Results The pemafibrate-treated group had markedly lower triglyceride deposition and lipid absorption in the intestine, and significantly lower levels of molecules involved in intestinal lipid regulation than the pemafibrate-untreated group. Moreover, hepatic fibrosis significantly improved, and the mRNA levels of fibrosis-related molecules and hepatic stellate cell activation factors significantly decreased in the pemafibrate-treated compared with those in the pemafibrate-untreated group. Conclusions Pemafibrate reduced lipid droplet formation and LCFA absorption in the intestinal tract and alleviated hepatic fibrosis in MASH model rats.
ISSN:1471-230X