2025
Intestinal L-cell mechanoreception regulates hepatic lipid metabolism through GLP-1
Publication Information
Title: Intestinal L-cell mechanoreception regulates hepatic lipid metabolism through GLP-1
Author(s):Luyang Gao,https://orcid.org/0009-0005-6735-5353，Ke Yang,Yawen Zhao,Jinshan Zhang,Shaohua Jiang,Rujiao Zhang,Wenxin He,Yuhang Zhao,Qianqian Ye
Geyang Xu*
Journal Name, Year, Volume(Issue): Page range:Science Advances,30 May 2025, Vol 11(22)
Abstract:Glucagon-like peptide–1 (GLP-1), secreted by intestinal L cells, is essential for lowering postprandial glucose levels and regulating hepatic lipid metabolism.We investigate the effects of manipulating Piezo1 in L cells on hepatic lipid metabolism. We found that normal and high-fat diet–fed L cell–specific Piezo1 knockout (IntL-Piezo1−/−) mice exhibited reduced circulating GLP-1 levels, increased hepatic lipid accumulation, decreased β-catenin expression, and elevated lipogenesis-related genes and proteins, including SREBP1c, PPARγ, FASN, and ACC. Treatment with exendin-4 improved fatty liver inIntL-Piezo1−/− mice by stimulating β-catenin and inhibiting de novo lipogenesis. Intestinal bead implantation stimulated GLP-1 release and inhibited lipid synthesis in livers of diet-induced obese mice but not inIntL-Piezo1−/− mice. In primary hepatocytes derived fromIntL-Piezo1−/− mice, lipid accumulation and enhanced fatty acid synthesis were associated with reduced β-catenin expression and impaired nuclear translocation. Exendin-4 treatment alleviated lipid accumulation, which was blocked by the β-catenin inhibitor nitazoxanide. L-cell mechanoreception is vital for regulating hepatic lipid metabolism through GLP-1.
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