Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Obesity (Silver Spring). 2014 Feb;22(2):390-400. doi: 10.1002/oby.20548. Epub 2013 Sep 5.
Our objective was to investigate the role of bile acids in hepatic steatosis reduction after vertical sleeve gastrectomy (VSG).
High fat diet (HFD)-induced obese C57Bl/6 mice were randomized to VSG, Sham operation (Sham), Sham operation with pair feeding to VSG (Sham-PF), or nonsurgical controls (Naïve). All mice were on HFD until sacrifice. Mice were observed postsurgery and data for body weight, body composition, metabolic parameters, serum bile acid level and composition were collected. Further hepatic gene expression by mRNA-seq and RT-PCR analysis was assessed.
VSG and Sham-PF mice lost equal weight postsurgery while VSG mice had the lowest hepatic triglyceride content at sacrifice. The VSG mice had elevated serum bile acid levels that positively correlated with maximal weight loss. Serum bile composition in the VSG group had increased cholic and tauroursodeoxycholic acid. These bile acid composition changes in VSG mice explained observed downregulation of hepatic lipogenic and bile acid synthetic genes.
VSG in obese mice results in greater hepatic steatosis reduction than seen with caloric restriction alone. VSG surgery increases serum bile acids that correlate with weight lost postsurgery and changes serum bile composition that could explain suppression of hepatic genes responsible for lipogenesis.
本研究旨在探讨胆汁酸在垂直袖状胃切除术（VSG）后肝脂肪变性减轻中的作用。
高脂饮食（HFD）诱导肥胖 C57Bl/6 小鼠随机分为 VSG、假手术（Sham）、VSG 配对喂养假手术（Sham-PF）或非手术对照（Naïve）组。所有小鼠均接受 HFD 喂养直至处死。观察术后小鼠体重、体成分、代谢参数、血清胆汁酸水平和组成，并进一步通过 mRNA-seq 和 RT-PCR 分析评估肝脏基因表达。
VSG 和 Sham-PF 术后体重减轻量相同，而 VSG 组在处死时肝脏甘油三酯含量最低。VSG 组血清胆汁酸水平升高，与最大体重减轻呈正相关。VSG 组血清胆汁酸组成中胆酸和牛磺熊脱氧胆酸增加。VSG 小鼠肝脏脂肪生成和胆汁酸合成基因的下调可以解释这些胆汁酸组成的变化。
与单纯热量限制相比，肥胖小鼠的 VSG 可导致更大程度的肝脂肪变性减轻。VSG 手术增加了血清胆汁酸，与术后体重减轻相关，并改变了血清胆汁酸组成，这可能解释了抑制肝脏中负责脂肪生成的基因的机制。
