减重手术对肥胖小鼠糖脂代谢的影响：基于转录组学与LC-MS非靶向代谢组学的分析

郭忠昊; 赵圣捷; 王玮; 李瑞斌

doi:10.11817/j.issn.1672-7347.2026.250564

您当前的位置：

首页 >

文章列表页 >

减重手术对肥胖小鼠糖脂代谢的影响：基于转录组学与LC-MS非靶向代谢组学的分析

移动端阅览

文章被引用时，请邮件提醒。

提交

论著 | 更新时间：2026-05-05

减重手术对肥胖小鼠糖脂代谢的影响：基于转录组学与LC-MS非靶向代谢组学的分析
Effects of bariatric surgery on glucose and lipid metabolism in obese mice: An integrated transcriptomic and LC-MS-based untargeted metabolomics analysis
中南大学学报(医学版) 中南大学学报(医学版) 2026年51卷第2期页码：228-239
作者机构：

1.内蒙古科技大学包头医学院第一附属医院腹部微创手术中心/日间手术中心，包头 014010
2.内蒙古科技大学包头医学院第一附属医院内分泌科，包头 014010
作者简介：

郭忠昊，Email: 1789757902@qq.com, ORCID: 0009-0004-0945-7717
王玮，博士，主任医师，Email: vvhappy521@163.com, ORCID: 0000-0001-6607-6137
李瑞斌，副主任医师，Email: 15849472388@163.com, ORCID: 0000-0002-5180-694X
基金信息：

内蒙古自治区自然科学基金(2023MS08048┫。This work was supported by the Natural Science Foundation;China ┣2023MS08048)
DOI：10.11817/j.issn.1672-7347.2026.250564
中图分类号：
CSTR：
收稿：2025-10-11，

纸质出版：2026-02-28
稿件说明：

郭忠昊, 赵圣捷, 王玮, 李瑞斌. 减重手术对肥胖小鼠糖脂代谢的影响：基于转录组学与LC-MS非靶向代谢组学的分析[J]. 中南大学学报(医学版), 2026, 51(2): 228-239.

GUO Zhonghao, ZHAO Shengjie, WANG Wei, LI Ruibin. Effects of bariatric surgery on glucose and lipid metabolism in obese mice: An integrated transcriptomic and LC-MS-based untargeted metabolomics analysis[J]. Journal of Central South University. Medical Science, 2026, 51(2): 228-239.
郭忠昊, 赵圣捷, 王玮, 李瑞斌. 减重手术对肥胖小鼠糖脂代谢的影响：基于转录组学与LC-MS非靶向代谢组学的分析[J]. 中南大学学报(医学版), 2026, 51(2): 228-239. DOI：10.11817/j.issn.1672-7347.2026.250564.

GUO Zhonghao, ZHAO Shengjie, WANG Wei, LI Ruibin. Effects of bariatric surgery on glucose and lipid metabolism in obese mice: An integrated transcriptomic and LC-MS-based untargeted metabolomics analysis[J]. Journal of Central South University. Medical Science, 2026, 51(2): 228-239. DOI：10.11817/j.issn.1672-7347.2026.250564.

摘要

目的

肥胖及其并发的糖脂代谢紊乱，其健康危害日益突出。减重手术是目前治疗重度肥胖及其代谢合并症的有效手段。本研究旨在探究减重手术对高脂饮食(high-fat diet，HFD)诱导的肥胖小鼠糖脂代谢的影响。

方法

构建肥胖小鼠模型。将4周龄雄性C57BL/6J小鼠(

=32)分为对照(control，CTL)组(

=8)、HFD组(

=24)。在小鼠20周龄时，将HFD组进一步分为3个亚组，每组8只：HFD-HFD组(不做特殊干预)、HFD-SHAM组(进行假手术)、HFD-袖状胃切除术(sleeve gastrectomy，SG)组(进行SG)。每周记录小鼠的体重和摄食量；分别在20周龄(术前)和24周龄(术后4周)对小鼠进行腹腔葡萄糖耐量试验(intraperitoneal glucose tolerance test，IPGTT)及腹腔胰岛素耐量试验(intraperitoneal insulin tolerance test，IPITT)；在24周龄时，采集禁食小鼠血液样本和米色、白色及棕色脂肪组织。血液样本用于测定血清中游离脂肪酸(free fatty acid，FFA)、总胆固醇(total cholesterol，TC)、甘油三酯(triglyceride，TG)及胰岛素水平。脂肪组织用于HFD-SHAM与HFD-SG组间差异表达基因和差异代谢物的筛选。对差异表达基因进行基因本体论(Gene Ontology，GO)功能富集分析和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路富集分析，对差异代谢物进行通路富集分析，并整合转录组与代谢组数据，分析相关联通路及相关基因的表达特征。

结果

在术后4周，相较于HFD-HFD组和HFD-SHAM组，HFD-SG组的体重及摄食量显著降低(均

0.05)；葡萄糖耐量及胰岛素耐量显著改善(均

0.05)；胰岛素、FFA、TC、TG水平均显著降低(均

0.05)。在脂肪组织转录组学分析中，HFD-SG组与HFD-SHAM组共鉴定出763个差异表达基因，其中384个上调、379个下调。GO及KEGG富集分析显示类固醇激素生物合成等通路被激活。代谢组学分析进一步筛选出16个差异代谢物，富集分析涉及抗坏血酸与醛糖二酸代谢、叶酸介导

的一碳代谢等通路。整合转录组与代谢组数据发现，类固醇激素生物合成及叶酸介导的一碳代谢通路HFD-SG组与HFD-SHAM组间存在关联。在类固醇生物合成通路中，

LSS

、

Nsdhl

、

DHCR24

、

Hsd17b7

、

MSMO1

、

SQLE

、

CYP51

等7个基因在HFD-SG组的3种脂肪组织中均呈上调趋势，而在HFD-SHAM组呈下调趋势；代谢物5-雄烯二醇在HFD-SG组中下调，与基因表达趋势相反。在叶酸介导的一碳代谢通路中，

Aldh1l2

、

GNMT

仅在HFD-SHAM组米色脂肪组织中上调，而

TYMS

、

Sardh

在HFD-SG组米色及白色脂肪组织中上调；代谢物脱氧胸苷-5’-单磷酸在HFD-SG组上调，与基因表达趋势一致。

结论

减重手术可显著降低HFD诱导的肥胖模型小鼠的体重与摄食量，改善其葡萄糖耐量和胰岛素耐量，纠正其紊乱的血脂代谢。手术可调节脂肪组织中类固醇生物合成及叶酸介导的一碳代谢通路，改变关键基因与代谢物的表达特征。减重手术通过重塑脂肪组织代谢相关通路系统性改善糖脂代谢，本研究为肥胖及相关代谢性疾病的治疗提供了新的分子依据。

Abstract

Objective

Obesity and its associated disorders of glucose and lipid metabolism have become increasingly significant public health concerns. Bariatric surgery is an effective intervention for severe obesity and related metabolic comorbidities. This study aims to investigate the effects of bariatric surgery on glucose and lipid metabolism in high-fat diet (HFD)-induced obese mice.

Methods

An obesity mouse model was established. Four-week-old male C57BL/6J mice (

=32) were randomly divided into a control (CTL) group (

=8) and an HFD group (

=24). At 20 weeks of age

HFD mice were further divided into 3 subgroups (

=8 per group): a HFD-HFD group

a sham-operated group (HFD-SHAM group)

and an HFD-sleeve gastrectomy (SG) group. Body weight and food intake were recorded weekly. Intraperitoneal glucose tolerance tests (IPGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed at 20 weeks (preoperatively) and 24 weeks (4 weeks postoperatively). At 24 weeks

fasting blood samples and beige

white

and brown adipose tissues were collected. Serum levels of free fatty acids (FFA)

total cholesterol (TC)

triglycerides (TG)

and insulin wer

e measured. Transcriptomic and metabolomic analyses were conducted to identify differentially expressed genes (DEGs) and differential metabolites between the HFD-SHAM and HFD-SG groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed

followed by integrative analysis of transcriptomic and metabolomic data.

Results

Four weeks after surgery

compared with the HFD-HFD and HFD-SHAM groups

the HFD-SG group showed significantly reduced body weight and food intake (all

0.05)

improved glucose tolerance and insulin sensitivity (both

0.05)

and decreased levels of insulin

free fatty acids (FFA)

total cholesterol (TC)

and triglycerides (TG) (all

0.05). Transcriptomic analysis identified 763 DEGs between the HFD-SG and HFD-SHAM groups

including 384 upregulated and 379 downregulated genes. GO and KEGG enrichment analyses revealed activation of pathways such as steroid hormone biosynthesis. Metabolomic analysis identified 16 differential metabolites enriched in pathways including ascorbate and aldarate metabolism and folate-mediated one-carbon metabolism. Integrative analysis revealed that steroid biosynthesis and folate-mediated one-carbon metabolism pathways were significantly associated between the two groups. In the steroid biosynthesis pathway

genes including

LSS

Nsdhl

DHCR24

Hsd17b7

MSMO1

SQLE

and

CYP51

were upregulated in all three adipose tissues in the HFD-SG group but downregulated in the HFD-SHAM group

whereas the metabolite androstenediol was decreased in the HFD-SG group. In the folate-mediated one-carbon metabolism pathway

Aldh1l2

and

GNMT

were upregulated only in beige adipose tissue of the HFD-SHAM group

while

TYMS

and

Sardh

were upregulated in beige and white

adipose tissues of the HFD-SG group. The metabolite deoxythymidine monophosphate was increased in the HFD-SG group

consistent with gene expression trends.

Conclusion

SG significantly reduced body weight and food intake

improved glucose tolerance and insulin sensitivity

and corrected lipid metabolism disorders in HFD-induced obese mice. Bariatric surgery regulates steroid biosynthesis and folate-mediated one-carbon metabolism pathways in adipose tissue

altering key gene and metabolite expression profiles. These findings suggest that bariatric surgery improves systemic glucose and lipid metabolism by remodeling metabolic pathways in adipose tissue

providing novel molecular insights for the treatment of obesity and related metabolic diseases.

关键词

Keywords

references

GBD 2021 Adult BMI Collaborators . Global, regional, and national prevalence of adult overweight and obesity, 1990-2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021 [J ] . Lancet , 2025 , 405 ( 10481 ): 813 - 838 . https://doi.org/10.1016/S0140-6736(25)00355-1 https://doi.org/10.1016/S0140-6736(25)00355-1 .

Madsbad S , Dirksen C , Holst JJ . Mechanisms of changes in glucose metabolism and bodyweight after bariatric surgery [J ] . Lancet Diabetes Endocrinol , 2014 , 2 ( 2 ): 152 - 164 . https://doi.org/10.1016/S2213-8587(13)70218-3 https://doi.org/10.1016/S2213-8587(13)70218-3 .

Wiggins T , Guidozzi N , Welbourn R , et al . Association of bariatric surgery with all-cause mortality and incidence of obesity-related disease at a population level: a systematic review and meta-analysis [J/OL ] . PLoS Med , 2020 , 17 ( 7 ): e 1003206 [ 2025-10-01 ] . https://doi.org/10.1371/journal.pmed.1003206 https://doi.org/10.1371/journal.pmed.1003206 .

苏志红 , 朱利勇 , 高祥 , 等 . 高胰岛素-正葡萄糖钳夹实验评价Roux-en-Y胃旁路术对2型糖尿病患者胰岛素抵抗的改善作用 [J ] . 中南大学学报(医学版) , 2021 , 46 ( 6 ): 609 - 614 . https://doi. org/10.11817/j.issn.1672-7347.2021.190771 https://doi.org/10.11817/j.issn.1672-7347.2021.190771 .

SU Zhihong , ZHU Liyong , GAO Xiang , et al . Effect of laparoscopic Roux-en-Y gastric bypass on improvement of insulin resistance in Type 2 diabetic patients evaluated by hyperinsulinemic-euglycemic clamp [J ] . Journal of Central South University (Medical Science) , 2021 , 46 ( 6 ): 609 - 614 . https://doi.org/10.11817/j.issn.1672-7347.2021.190771 https://doi.org/10.11817/j.issn.1672-7347.2021.190771 .

Angrisani L , Santonicola A , Iovino P , et al . IFSO worldwide survey 2020-2021: current trends for bariatric and metabolic procedures [J ] . Obes Surg , 2024 , 34 ( 4 ): 1075 - 1085 . https://doi.org/10.1007/s11695-024-07118-3 https://doi.org/10.1007/s11695-024-07118-3 .

Huang RH , Ding XS , Fu HB , et al . Potential mechanisms of sleeve gastrectomy for reducing weight and improving metabolism in patients with obesity [J ] . Surg Obes Relat Dis , 2019 , 15 ( 10 ): 1861 - 1871 . https://doi.org/10.1016/j.soard.2019. 06.022 https://doi.org/10.1016/j.soard.2019.06.022 .

Liu CX , Xu Q , Dong SH , et al . New mechanistic insights of anti-obesity by sleeve gastrectomy-altered gut microbiota and lipid metabolism [J ] . Front Endocrinol , 2024 , 15 : 1338147 . https://doi.org/10.3389/fendo.2024.1338147 https://doi.org/10.3389/fendo.2024.1338147 .

Hu JY , Wang MF , Zhou Y , et al . Bariatric surgery in rats upregulates FSP27 expression in fat tissue to affect fat hydrolysis and metabolism [J ] . Biomed Res Int , 2019 , 2019 : 6415732 . https://doi.org/10.1155/2019/6415732 https://doi.org/10.1155/2019/6415732 .

Soares GM , Lopes LES , Balbo SL , et al . Sleeve gastrectomy-induced weight loss increases insulin clearance in obese mice [J ] . Int J Mol Sci , 2023 , 24 ( 2 ): 1729 . https://doi.org/10. 3390/ijms24021729 https://doi.org/10.3390/ijms24021729 .

Cho CH , Patel S , Rajbhandari P . Adipose tissue lipid metabolism: lipolysis [J ] . Curr Opin Genet Dev , 2023 , 83 : 102114 . https://doi.org/10.1016/j.gde.2023.102114 https://doi.org/10.1016/j.gde.2023.102114 .

Hierons SJ , Abbas K , Sobczak AIS , et al . Changes in plasma free fatty acids in obese patients before and after bariatric surgery highlight alterations in lipid metabolism [J ] . Sci Rep , 2022 , 12 ( 1 ): 15337 . https://doi.org/10.1038/s41598-022-19657-9 https://doi.org/10.1038/s41598-022-19657-9 .

Heffron SP , Parikh A , Volodarskiy A , et al . Changes in lipid profile of obese patients following contemporary bariatric surgery: a meta-analysis [J ] . Am J Med , 2016 , 129 ( 9 ): 952 - 959 . https://doi.org/10.1016/j.amjmed.2016.02.004 https://doi.org/10.1016/j.amjmed.2016.02.004 .

Chang E , Kim Y . Vitamin D insufficiency exacerbates adipose tissue macrophage infiltration and decreases AMPK/SIRT1 activity in obese rats [J ] . Nutrients , 2017 , 9 ( 4 ): 338 . https://doi.org/10.3390/nu9040338 https://doi.org/10.3390/nu9040338 .

Zhang J , Feng M , Pan LS , et al . Effects of vitamin D deficiency on the improvement of metabolic disorders in obese mice after vertical sleeve gastrectomy [J ] . Sci Rep , 2021 , 11 ( 1 ): 6036 . https://doi.org/10.1038/s41598-021-85531-9 https://doi.org/10.1038/s41598-021-85531-9 .

Pu LY , Meng QY , Li S , et al . Laminar shear stress alleviates monocyte adhesion and atherosclerosis development via miR-29b-3p/CX3CL1 axis regulation [J/OL ] . J Cell Sci , 2022 , 135 ( 14 ): jcs259696[ 2025-10-01 ] . https://doi.org/10.1242/jcs.259696 https://doi.org/10.1242/jcs.259696 .

Wang CH , Tao QM , Wang XH , et al . Impact of high-fat diet on liver genes expression profiles in mice model of nonalcoholic fatty liver disease [J ] . Environ Toxicol Pharmacol , 2016 , 45 : 52 - 62 . https://doi.org/10.1016/j.etap.2016.05.014 https://doi.org/10.1016/j.etap.2016.05.014 .

Li Y , Wang C , Jin Y , et al . Huang-Qi San improves glucose and lipid metabolism and exerts protective effects against hepatic steatosis in high fat diet-fed rats [J ] . Biomed Pharmacother , 2020 , 126 : 109734 . https://doi.org/10.1016/j.biopha.2019.109734 https://doi.org/10.1016/j.biopha.2019.109734 .

Xin Y , Li C , Guo Y , et al . RNA-Seq analysis reveals a negative role of MSMO1 with a synergized NSDHL expression during adipogenesis of 3T3-L1 [J ] . Biosci Biotechnol Biochem , 2019 , 83 ( 4 ): 641 - 652 . https://doi.org/10.1080/09168451.2018.1559719 https://doi.org/10.1080/09168451.2018.1559719 .

Chen X , Deng SZ , Sun Y , et al . Key genes involved in nonalcoholic steatohepatitis improvement after bariatric surgery [J ] . Front Endocrinol , 2024 , 15 : 1338889 . https://doi.org/10. 3389/fendo.2024.1338889 https://doi.org/10.3389/fendo.2024.1338889 .

Ducker GS , Rabinowitz JD . One-carbon metabolism in health and disease [J ] . Cell Metab , 2017 , 25 ( 1 ): 27 - 42 . https://doi.org/10. 1016/j.cmet.2016.08.009 https://doi.org/10.1016/j.cmet.2016.08.009 .

浏览量

下载量

CSCD

工具集

关联资源

基于多组学技术探讨中药黄酮类化合物在疾病治疗中的应用

结合多组学和机器学习构建多发性骨髓瘤疗效预测模型

组学技术在肿瘤耐药领域的研究进展：从单组学到多组学联合应用

肠道菌群与代谢在慢性荨麻疹发病机制中的研究进展

单细胞RNA测序技术在乳腺发育及相关疾病中的应用进展