Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.
Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, PR China.
Biochem Biophys Res Commun. 2024 May 28;710:149882. doi: 10.1016/j.bbrc.2024.149882. Epub 2024 Apr 3.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease associated with type 2 diabetes mellitus (T2D). NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and even cancer, all of which have a very poor prognosis. Semaglutide, a novel glucagon-like peptide-1 (GLP-1) receptor agonist, has been recognized as a specific drug for the treatment of diabetes. In this study, we used a gene mutation mouse model (db/db mice) to investigate the potential liver-improving effects of semaglutide. The results showed that semaglutide improved lipid levels and glucose metabolism in db/db mice. HE staining and oil red staining showed alleviation of liver damage and reduction of hepatic lipid deposition after injection of semaglutide. In addition, semaglutide also improved the integrity of gut barrier and altered gut microbiota, especially Alloprevotella, Alistpes, Ligilactobacillus and Lactobacillus. In summary, our findings validate that semaglutide induces modifications in the composition of the gut microbiota and ameliorates NAFLD, positioning it as a promising therapeutic candidate for addressing hepatic steatosis and associated inflammation.
非酒精性脂肪性肝病（NAFLD）是与 2 型糖尿病（T2D）相关的最常见的肝脏疾病。NAFLD 可进展为非酒精性脂肪性肝炎（NASH）、肝硬化，甚至肝癌，所有这些疾病的预后都非常差。司美格鲁肽，一种新型胰高血糖素样肽-1（GLP-1）受体激动剂，已被认为是治疗糖尿病的特定药物。在这项研究中，我们使用基因突变异种小鼠模型（db/db 小鼠）来研究司美格鲁肽对肝脏的潜在改善作用。结果表明，司美格鲁肽改善了 db/db 小鼠的血脂水平和葡萄糖代谢。HE 染色和油红染色显示，注射司美格鲁肽后，肝损伤减轻，肝脂质沉积减少。此外，司美格鲁肽还改善了肠道屏障的完整性，并改变了肠道微生物群，特别是 Alloprevotella、Alistpes、Ligilactobacillus 和 Lactobacillus。总之，我们的研究结果证实，司美格鲁肽可诱导肠道微生物群组成的改变，并改善 NAFLD，使其成为治疗肝脂肪变性和相关炎症的有前途的治疗候选药物。
