肥胖男童尿液差异代谢物的筛选

刘韦, 董洁, 高超男, 齐千瑾, 孔亚伟, 孟鑫, 彭晓霞, 闫银坤

中国儿童保健杂志 ›› 2025, Vol. 33 ›› Issue (2) : 180-184.

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中国儿童保健杂志 ›› 2025, Vol. 33 ›› Issue (2) : 180-184. DOI: 10.11852/zgetbjzz2024-0654
科研论著

肥胖男童尿液差异代谢物的筛选

  • 刘韦1*, 董洁2*, 高超男1, 齐千瑾1, 孔亚伟1, 孟鑫1, 彭晓霞3, 闫银坤1
作者信息 +

Screening of differential metabolites in the urine of obese boys

  • LIU Wei1*, DONG Jie2*, GAO Chaonan1, QI Qianjin1, KONG Yawei1, MENG Xin1, PENG Xiaoxia3, YAN Yinkun1
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文章历史 +

摘要

目的 探究肥胖男童与体重正常男童之间尿液代谢物特征的差异,为肥胖的发病机制提供初步线索。方法 采用病例对照研究设计,于2021年9—10月在湖南长沙三所寄宿学校招募6~14岁儿童,按体重状态分为肥胖组和体重正常组,将两组儿童按年龄1∶1进行匹配,最终纳入10名正常体重男童和10名肥胖男童。连续收集3d 24h尿样,混匀后取2mL尿样进行靶向检测。采用正交偏最小二乘法判别分析比较两组间代谢物的整体组成差异、t检验和差异倍数值相结合的方法筛选差异代谢物。结果 肥胖组中吲哚-3-甲基乙酸酯、吲哚-3-丙酸、吲哚乙酸、胆酸、乙酰胆碱酸、石胆酸-3-硫酸盐、7-酮去氢胆酸、甲基半胱氨酸、脯氨酸和癸二酸的水平低于正常体重组,差异有统计学意义(Log2FC≤-0.5,P<0.05)。结论 肥胖男童与体重正常男童的尿液代谢物存在差异,可为肥胖的预防和控制提供新线索。

Abstract

Objective To investigate the differences in urinary metabolite profiles between obese and normal-weight boys, in order to provide preliminary clues for understanding the pathogenesis of obesity. Methods A case-control study design was employed. From September to October 2021, children aged 6 - 14 years were recruited from three boarding schools in Changsha, Hunan. Participants were divided into obese and normal-weight groups based on their weight status. Ten normal-weight boys and ten obese boys were matched by age(1∶1 ratio).24-hour urine samples were collected continuously for three days, mixed, and 2mL of urine was taken for targeted detection. Orthogonal partial least squares discriminant analysis(OPLS-DA) was used to compare the overall differences in metabolite composition between the two groups, and a combination of t-test and fold change(FC) values was employed to screen for differential metabolites. Result The levels of Indole-3-methyl acetate, Indole-3-propionic acid, Indoleacetic acid, Cholic acid, Glycocholic acid, Sulfated lithocholic acid, 7-dehydrocholic acid, Methylcysteine, Proline, and Sebacic acid were significantly lower in the obese group compared to the normal-weight group(Log2FC≤-0.5, P <0.05). Conclusion Differences in urine metabolites exist between obese and normal-weight male children, which may provide new clues for the prevention and control of obesity.

关键词

肥胖 / 差异代谢物 / 尿液 / 代谢组学

Key words

obesity / differential metabolites / urine / metabolomics

引用本文

导出引用
刘韦, 董洁, 高超男, 齐千瑾, 孔亚伟, 孟鑫, 彭晓霞, 闫银坤. 肥胖男童尿液差异代谢物的筛选[J]. 中国儿童保健杂志. 2025, 33(2): 180-184 https://doi.org/10.11852/zgetbjzz2024-0654
LIU Wei, DONG Jie, GAO Chaonan, QI Qianjin, KONG Yawei, MENG Xin, PENG Xiaoxia, YAN Yinkun. Screening of differential metabolites in the urine of obese boys[J]. Chinese Journal of Child Health Care. 2025, 33(2): 180-184 https://doi.org/10.11852/zgetbjzz2024-0654
中图分类号: R723.14   

参考文献

[1] Zhang X, Liu J, Ni Y, et al. Global prevalence of overweight and obesity in children and adolescents: A systematic review and Meta-analysis[J]. JAMA Pediatr, 2024, 178(8): 800-813.
[2] Twig G, Yaniv G, Levine H, et al. Body mass index in 2.3 million adolescents and cardiovascular death in adulthood[J]. N Engl J Med, 2016, 374(25): 2430-2340.
[3] Piché ME, Tchernof A, Després JP. Obesity phenotypes, diabetes, and cardiovascular diseases[J]. Circ Res, 2020, 126(11): 1477-1500.
[4] Younossi Z, Tacke F, Arrese M, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Hepatology, 2019, 69(6): 2672-2682.
[5] Kovesdy CP, Furth SL, Zoccali C. Obesity and kidney disease: Hidden consequences of the epidemic[J]. J Nephrol, 2017, 30(1): 1-10.
[6] 原晨晨. 全球儿童超重肥胖的流行现状和影响因素[J]. 卫生研究, 2020, 49(3): 506-511.
Yuan CC. Global prevalence and influencing factors of childhood overweight and obesity[J]. Health Research, 2020, 49(3): 506-511.(in Chinese)
[7] Reddon H, Guéant JL, Meyre D. The importance of gene-environment interactions in human obesity[J]. Clin Sci(Lond), 2016, 130(18): 1571-1597.
[8] Jacob M, Lopata AL, Dasouki M, et al. Metabolomics toward personalized medicine[J]. Mass Spectrom Rev, 2019, 38(3): 221-238.
[9] Wishart DS. Emerging applications of metabolomics in drug discovery and precision medicine[J]. Nat Rev Drug Discov, 2016, 15(7): 473-484.
[10] Chan ECY, Pasikanti KK, Nicholson JK. Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry[J]. Nature Protocols, 2011, 6(10): 1483-1499.
[11] 聂倩, 张令霞, 宋光耀. 尿液代谢组学与代谢性疾病生物标志物的研究进展[J]. 中华糖尿病杂志, 2023, 15(10): 1016-1020.
Nie Q, Zhang LX, Song GY. Research progress on urine metabolomics and biomarkers of metabolic diseases[J]. Chin J Diabetes Mellitus, 2023, 15(10): 1016-1020.(in Chinese)
[12] 刘璐洁, 徐东, 尹春燕, 等. 儿童肥胖代谢组学的研究进展[J]. 中国儿童保健杂志, 2024, 32(8): 881-885.
Liu LJ,Xu D,Yin CY,et al. Research progress on metabolomics of childhood obesity[J]. Chin J Child Health Care, 2024, 32(8): 881-885.(in Chinese)
[13] Cho K, Moon JS, Kang JH, et al. Combined untargeted and targeted metabolomic profiling reveals urinary biomarkers for discriminating obese from normal-weight adolescents[J]. Pediatr Obes, 2017, 12(2): 93-101.
[14] Cole TJ, Lobstein T. Extended international(IOTF) body mass index cut-offs for thinness, overweight and obesity[J]. Pediatr Obes, 2012, 7(4): 284-294.
[15] Agus A, Planchais J, Sokol H. Gut microbiota regulation of tryptophan metabolism in health and disease[J]. Cell HostMicrobe, 2018, 23(6): 716-724.
[16] Chimerel C, Emery E, Summers DK, et al. Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells[J]. Cell Rep, 2014, 9(4): 1202-1208.
[17] Modoux M, Rolhion N, Mani S, et al. Tryptophan metabolism as a pharmacological target[J]. Trends Pharmacol Sci, 2021, 42(1): 60-73.
[18] Li X, Yang J, Zhou X, et al. Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption[J]. Nat Metab, 2024, 6(7): 1397-1414.
[19] Chávez-Talavera O, Tailleux A, Lefebvre P, et al. Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease[J]. Gastroenterology, 2017, 152(7): 1679-1694.e3.
[20] Yamada S, Kawaguchi H, Yamada T, et al. Cholic acid enhances visceral adiposity, atherosclerosis and nonalcoholic fatty liver disease in microminipigs[J]. J Atheroscler Thromb, 2017, 24(11): 1150-1166.
[21] Lou G, Ma X, Fu X, et al. GPBAR1/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells[J]. PLoS One, 2014, 9(4): e93567.
[22] Petersen A, Julienne H, Hyötyläinen T, et al. Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species[J]. Sci Rep, 2021, 11(1): 13252.
[23] Watanabe M, Horai Y, Houten SM, et al. Lowering bile acid pool size with a synthetic farnesoid X receptor(FXR) agonist induces obesity and diabetes through reduced energy expenditure[J]. J Biol Chem, 2011, 286(30): 26913-26920.
[24] Bathena SP, Thakare R, Gautam N, et al. Urinary bile acids as biomarkers for liver diseases II. Signature profiles in patients[J]. Toxicol Sci, 2015, 143(2): 308-318.
[25] 金红芳, 杨晓征, 刘颖, 等. 肥胖儿童含硫氨基酸体系的变化[J]. 实用儿科临床杂志, 2008, 23(20): 1566-1568.
Jin HF,Yang XZ,Liu Y,et al. Changes in the sulfur amino acid system in obese children[J]. Chin J Pract Pediatr, 2008, 23(20): 1566-1568.(in Chinese)
[26] 张清友, 杜军保, 石琳, 等. 内源性一氧化氮与硫化氢在大鼠低氧性肺动脉高压中的相互作用[J]. 北京大学学报(医学版), 2004, 36(1): 52-56.
Zhang QY,Du JB, Shi L, et al. Interaction between endogenous nitric oxide and hydrogen sulfide in hypoxic pulmonary hypertension in rats[J]. J Peking Univ, 2004, 36(1): 52-56.(in Chinese)
[27] Huang CN, Horng JS, Yin MC. Antioxidative and antiglycative effects of six organosulfur compounds in low-density lipoprotein and plasma[J]. J Agric Food Chem, 2004, 52(11): 3674-3678.
[28] Hsu CC, Huang CN, Hung YC, et al. Five cysteine-containing compounds have antioxidative activity in Balb/cA mice[J]. J Nutr, 2004, 134(1): 149-152.
[29] Christgen SL, Becker DF. Role of proline in pathogen and host interactions[J]. Antioxid Redox Signal, 2019, 30(4): 683-709.
[30] Xia B, Zhu Q, Zhao Y, et al. Phthalate exposure and childhood overweight and obesity: Urinary metabolomic evidence[J]. Environ Int, 2018, 121(Pt 1): 159-168.
[31] Zhou Y, Qiu L, Xiao Q, et al. Obesity and diabetes related plasma amino acid alterations[J]. Clin Biochem, 2013, 46(15): 1447-1452.
[32] Wu G. Amino acids: Metabolism, functions, and nutrition[J]. Amino Acids, 2009, 37(1): 1-17.
[33] Zhao J, Hu J, Ma X. Sodium caprylate improves intestinal mucosal barrier function and antioxidant capacity by altering gut microbial metabolism[J]. Food Funct, 2021, 12(20): 9750-9762.
[34] Liu L, Zhao J, Zhang R, et al. Serum untargeted metabolomics delineates the metabolic status in different subtypes of non-alcoholic fatty liver disease[J]. J Pharm Biomed Anal, 2021, 200: 114058.
[35] Membrez M, Chou CJ, Raymond F, et al. Six weeks′ sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice[J]. Diabetes Obes Metab, 2010, 12(12): 1120-1126.

基金

北京新星计划(Z201100006820008);湖南省自然科学基金(2022J40198);国家自然科学基金(81803254, 81973110, 82073572)

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