Yu Wang1, Geng Wang1, Jie Bai1, Ning Zhao1, Qingbo Wang1, Rui Zhou2, Gang Li1, Chaojie Hu3, Xin Li4, Kaixiong Tao1, Zefeng Xia5, Guobin Wang6. 1. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 2. Department of Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 3. Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 4. Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. 5. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xiazefeng0521@sina.com. 6. Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. tumorimmune973@126.com.
Abstract
BACKGROUND: This study aimed to investigate the weight-independent mechanism of sleeve gastrectomy on the relief of nonalcoholic fatty liver disease (NAFLD). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: This study aimed to investigate the weight-independent mechanism of sleeve gastrectomy on the relief of nonalcoholic fatty liver disease (NAFLD). METHODS: A total of 58 obesepatients 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Keith M Wirth; Adam C Sheka; Scott Kizy; Ryan Irey; Ashley Benner; Gretchen Sieger; Gyorgy Simon; Sisi Ma; John Lake; Constantin Aliferis; Daniel Leslie; Schelomo Marmor; Sayeed Ikramuddin Journal: Ann Surg Date: 2020-07 Impact factor: 12.969
Authors: Detlef Schuppan; Henning Grønbæk; Konstantin Kazankov; Simon Mark Dahl Jørgensen; Karen Louise Thomsen; Holger Jon Møller; Hendrik Vilstrup; Jacob George Journal: Nat Rev Gastroenterol Hepatol Date: 2019-03 Impact factor: 46.802