Department of Endocrinology, West China Hospital, Sichuan University, Chengdu.
From the Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai.
Pancreas. 2024 Feb 1;53(2):e157-e163. doi: 10.1097/MPA.0000000000002281. Epub 2024 Jan 15.
To explore the effects of branched-chain amino acids (BCAAs) on nonalcoholic fatty pancreas disease (NAFPD) and its possible mechanism in high-fat diet (HFD) induced mice.
Pancreatic morphology and lipid infiltration was assessed by hematoxylin-eosin staining and immunohistochemistry, and lipid levels in the pancreas were determined using colorimetric enzymatic method. Relevant mechanism was investigated using western blotting and biochemical test.
In HFD-fed mice, dietary BCAAs restriction could attenuate body weight increase, improve glucose metabolism, and reduce excessive lipid accumulation in the pancreas. Furthermore, expression of AMPKα and downstream uncoupling protein 1 were upregulated, while genes related to mammalian target of rapamycin complex 1 (mTORC1) signal pathway and lipid de novo synthesis were suppressed in HFD-BCAA restriction group compared with HFD and HFD-high BCAAs fed mice. In addition, BCAA restriction upregulated expression of BCAAs related metabolic enzymes including PPM1K and BCKDHA, and decreased the levels of BCAAs and branched chain keto acid in the pancreas. However, there was no difference in levels of lipid content in the pancreas and gene expression of AMPKα and mTORC1 between HFD and HFD-high BCAAs groups.
Branched-chain amino acid restriction ameliorated HFD-induced NAFPD in mice by activation of AMPKα pathway and suppression of mTORC1 pathway.
探讨支链氨基酸（BCAAs）对高脂饮食（HFD）诱导的非酒精性脂肪性胰腺疾病（NAFPD）的影响及其可能机制。
通过苏木精-伊红染色和免疫组织化学评估胰腺形态和脂质浸润，并使用比色酶学法测定胰腺中的脂质水平。使用 Western 印迹和生化试验研究相关机制。
在 HFD 喂养的小鼠中，限制饮食中的 BCAAs 可减轻体重增加，改善葡萄糖代谢，并减少胰腺中过多的脂质积累。此外，与 HFD 和 HFD-高 BCAAs 喂养的小鼠相比，HFD-BCAA 限制组中 AMPKα 的表达及其下游解偶联蛋白 1 上调，而与哺乳动物雷帕霉素靶蛋白复合物 1（mTORC1）信号通路和脂质从头合成相关的基因受到抑制。此外，BCAA 限制上调了包括 PPM1K 和 BCKDHA 在内的 BCAAs 相关代谢酶的表达，并降低了胰腺中 BCAAs 和支链酮酸的水平。然而，HFD 和 HFD-高 BCAAs 组之间胰腺中脂质含量和 AMPKα 和 mTORC1 的基因表达没有差异。
通过激活 AMPKα 通路和抑制 mTORC1 通路，限制支链氨基酸可改善 HFD 诱导的小鼠 NAFPD。
