Department of Surgery, James A. Haley Veterans Affairs Medical Center, University of South Florida, C/O Tampa General Hospital, P.O. Box 1289, Tampa, FL 33606, USA.
J Gastrointest Surg. 2010 Feb;14(2):221-8. doi: 10.1007/s11605-009-1102-5.
Roux-en-Y gastric bypass (RYGB) improves steatosis and reduces liver triglycerides in obese rats. Sirtuin1 (SIRT1) and AMP-activated protein kinase (AMPK) are key metabolic regulators that reduce lipogenesis and increase fatty acid oxidation. LKB1 phosphorylates AMPK and may activate SIRT1. We hypothesize that RYGB in obese rats is associated with an upregulation of the LKB1-AMPK-SIRT1 signaling pathway.
Obese Sprague-Dawley male rats underwent RYGB or sham. Liver tissue was obtained at 9 weeks postoperatively. Protein levels of SIRT1, LKB1, p-LKB1, AMPKalpha, p-AMPKalpha, and p-protein kinase C-zeta (PKC-zeta ) were determined. Protein associations of LKB1 with each of SIRT1, AMPKalpha, and PKC-zeta were determined by coimmunoprecipitation.Data are mean +/- SD; for t test, p<0.05 was significant.
RYGB increased protein levels of hepatic AMPKalpha, p-AMPKalpha, and SIRT1 (all p<0.001 vs. sham); p-LKB1 but not LKB1 increased after RYGB (p<0.001 vs. sham). Physical interactions of LKB1-AMPK and LKB1-SIRT1 increased after RYGB (p<0.001 vs. sham). Although PKC-zeta mRNA and p-PKC-zeta did not change, interactions between LKB1 and PKC-zeta increased after RYGB (p<0.001 vs. sham).
RYGB increases hepatic levels of SIRT1, AMPK, and p-AMPK as well as increasing interactions of LKB1 with AMPK or SIRT1. p-PKC-zeta may play an intermediary role in the interaction between AMPK and SIRT. These findings demonstrate key signaling changes in powerful metabolic regulators that may account for the resolution of steatosis after RYGB.
Roux-en-Y 胃旁路术（RYGB）可改善肥胖大鼠的脂肪变性并降低肝甘油三酯。沉默信息调节因子 1（SIRT1）和 AMP 激活的蛋白激酶（AMPK）是减少脂肪生成和增加脂肪酸氧化的关键代谢调节剂。LKB1 磷酸化 AMPK 并可能激活 SIRT1。我们假设肥胖大鼠的 RYGB 与 LKB1-AMPK-SIRT1 信号通路的上调有关。
肥胖的 Sprague-Dawley 雄性大鼠接受 RYGB 或假手术。术后 9 周获取肝组织。测定 SIRT1、LKB1、p-LKB1、AMPKalpha、p-AMPKalpha 和 p-蛋白激酶 C-zeta（PKC-zeta）的蛋白水平。通过免疫共沉淀测定 LKB1 与 SIRT1、AMPKalpha 和 PKC-zeta 的蛋白相互作用。数据为平均值 +/- SD；t 检验，p<0.05 为显著差异。
RYGB 增加了肝 AMPKalpha、p-AMPKalpha 和 SIRT1 的蛋白水平（均 p<0.001 与 sham 组相比）；RYGB 后 p-LKB1 而非 LKB1 增加（p<0.001 与 sham 组相比）。RYGB 后 LKB1-AMPK 和 LKB1-SIRT1 的物理相互作用增加（p<0.001 与 sham 组相比）。尽管 PKC-zeta mRNA 和 p-PKC-zeta 没有变化，但 RYGB 后 LKB1 与 PKC-zeta 的相互作用增加（p<0.001 与 sham 组相比）。
RYGB 增加了 SIRT1、AMPK 和 p-AMPK 的肝水平，并增加了 LKB1 与 AMPK 或 SIRT1 的相互作用。p-PKC-zeta 可能在 AMPK 和 SIRT 之间的相互作用中发挥中介作用。这些发现表明，强大的代谢调节剂中的关键信号变化可能解释了 RYGB 后脂肪变性的解决。
