Increase in bile acids after sleeve gastrectomy improves metabolism by activating GPBAR1 to increase cAMP in mice with nonalcoholic fatty liver disease

IF 3.1 4区医学 Q3 IMMUNOLOGY Immunity, Inflammation and Disease Pub Date : 2024-07-19 DOI:10.1002/iid3.1149

Guoliang Li, Xin Xu, Lixin Chai, Qunhao Guo, Wei Wu

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Abstract

Background

Bile acids (BAs) concentration can affect metabolic improvement caused by bariatric surgery and BA concentrations increase in patients after sleeve gastrectomy (SG). Here, how BAs after SG affect metabolism in nonalcoholic fatty liver disease (NAFLD) was studied.

Methods

Mice were given high-fat diet (HFD) to induce NAFLD and received SG surgery. Hepatic and fecal BA concentrations in mice were detected by liquid chromatography-tandem mass spectrometry method. BA-related genes were detected by quantitative real-time polymerase chain reaction. G protein BA receptor 1 (GPBAR1) expression was identified using western blot analysis. NAFLD mice after SG received GPBAR1 inhibitor Triamterene. The weight of mice and mice liver was detected. Mouse liver tissue was observed by hematoxylin–eosin and Oil Red O staining. Triglyceride (TG), nonesterified fatty acid (NEFA), and cyclic adenosine monophosphate (cAMP) levels in mouse liver tissue were analyzed by metabolic assay and enzyme-linked immune sorbent assay.

Results

SG boosted increase in hepatic total/conjugated BAs and related genes and GPBAR1 expression, and attenuated increase in fecal total BAs/muricholic acid in HFD-induced mice and increased fecal taurine-BAs in HFD-induced mice. Triamterene (72 mg/kg) reversed the inhibitory role of SG in HFD-induced increase of body weight, lipid accumulation, inflammatory cell infiltration, and increase of hepatic weight and TG/NEFA content, and counteracted the positive role of SG in HFD-induced increase of hepatic cAMP concentration in mice.

Conclusions

BAs improve metabolism via activating GPBAR1 to increase cAMP in NAFLD mice after SG.

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袖带胃切除术后胆汁酸的增加可通过激活 GPBAR1 增加非酒精性脂肪肝小鼠体内的 cAMP 来改善新陈代谢

背景胆汁酸（BAs）浓度会影响减肥手术对代谢的改善，袖带胃切除术（SG）后患者体内的胆汁酸浓度会增加。本文研究了袖带胃切除术后胆汁酸如何影响非酒精性脂肪肝（NAFLD）的代谢。方法给予小鼠高脂饮食（HFD）以诱导非酒精性脂肪肝，并让其接受 SG 手术。采用液相色谱-串联质谱法检测小鼠肝脏和粪便中的 BA 浓度。通过实时定量聚合酶链反应检测BA相关基因。通过 Western 印迹分析确定了 G 蛋白 BA 受体 1 (GPBAR1) 的表达。SG后的NAFLD小鼠接受GPBAR1抑制剂Triamterene治疗。检测小鼠和小鼠肝脏的重量。用苏木精-伊红和油红 O 染色观察小鼠肝组织。通过代谢测定和酶联免疫吸附测定分析小鼠肝组织中甘油三酯（TG）、非酯化脂肪酸（NEFA）和环磷酸腺苷（cAMP）的水平。结果 SG 促进了肝脏总/结合乙酰胆碱和相关基因及 GPBAR1 表达的增加，并减缓了高氟酸脱氢诱导型小鼠粪便中总乙酰胆碱/熊果酸的增加，以及高氟酸脱氢诱导型小鼠粪便中牛磺酸-乙酰胆碱的增加。曲安奈德（72 毫克/千克）逆转了 SG 在 HFD 诱导的体重增加、脂质积累、炎症细胞浸润以及肝脏重量和 TG/NEFA 含量增加中的抑制作用，并抵消了 SG 在 HFD 诱导的小鼠肝脏 cAMP 浓度增加中的积极作用。结论 BAs 可通过激活 GPBAR1 来增加 SG 后非酒精性脂肪肝小鼠体内的 cAMP，从而改善新陈代谢。

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来源期刊

Immunity, Inflammation and Disease Medicine-Immunology and Allergy

CiteScore

3.60

自引率

0.00%

发文量

146

审稿时长

8 weeks

期刊介绍： Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology