Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Obes Surg. 2021 Jul;31(7):3040-3052. doi: 10.1007/s11695-021-05321-0. Epub 2021 May 10.
This study aimed to investigate the weight-independent mechanism of sleeve gastrectomy on the relief of nonalcoholic fatty liver disease (NAFLD).
A total of 58 obese patients who had undergone sleeve gastrostomy (SG) were recruited. Plasma levels of indole-3-acetic acid (I3A), a metabolite from gut microbiota before and after SG were investigated. In addition, we had 78 C57BL/6J mice included in the study. High-fat diet (HFD) was used to induce obesity in mice. Sleeve gastrectomy (SG) was then performed. The liver of the mice was analyzed by HE and oil red staining to study lipid accumulation. Fluorescence-activated cell sorting (FACS) analysis was performed to study the phenotype of macrophages in the liver. The levels of I3A in serum, stool, and liver were tested by ELISA. Macrophages and hepatocytes were cultured in vitro and stimulated with I3A to study the effects on differentiation and proliferation/apoptosis.
In human samples, I3A increased after SG and plasma I3A levels were positively correlated with liver CT values and negatively correlated with liver fat attenuation. In mice models, after surgery, the percentage of M2 macrophages significantly increased in the liver. Both oral gavage and in vitro stimulation of I3A could promote M2 differentiation and did not significantly affect the state of hepatocytes.
This study suggested that increased I3A from the intestine after SG could reduce the M1/M2 ratio in the liver and thus promote relief of NAFLD in obese individuals. Graphical Abstract.
本研究旨在探讨袖状胃切除术减轻非酒精性脂肪性肝病（NAFLD）的体重独立机制。
共招募了 58 例接受袖状胃切除术（SG）的肥胖患者。研究了 SG 前后肠道微生物群的吲哚-3-乙酸（I3A）代谢物在血浆中的水平。此外，我们还纳入了 78 只 C57BL/6J 小鼠。使用高脂肪饮食（HFD）诱导小鼠肥胖，然后进行袖状胃切除术（SG）。通过 HE 和油红染色分析小鼠肝脏，研究脂质积累。采用荧光激活细胞分选（FACS）分析研究肝脏中巨噬细胞的表型。通过 ELISA 检测血清、粪便和肝脏中的 I3A 水平。体外培养巨噬细胞和肝细胞，用 I3A 刺激，研究其对分化和增殖/凋亡的影响。
在人体样本中，SG 后 I3A 增加，血浆 I3A 水平与肝脏 CT 值呈正相关，与肝脏脂肪衰减呈负相关。在小鼠模型中，手术后肝脏中 M2 巨噬细胞的比例明显增加。口服灌胃和体外刺激 I3A 均可促进 M2 分化，且对肝细胞状态无明显影响。
本研究表明，SG 后肠道中 I3A 的增加可以降低肝脏中 M1/M2 比值，从而促进肥胖个体中 NAFLD 的缓解。图表摘要。
