目的 系统评价成人代谢健康型肥胖(MHO)与各炎症因子的相关性,为肥胖炎症的早期血清学预警提供依据。方法 检索中国知网、万方、维普、中国生物医学文献数据库、PubMed、Web of Science、Embase、Cochrane Library中有关MHO与炎症因子水平的横断面研究,设定发表时限由建库至 2024-08-03;运用美国医疗保健研究与质量局的偏倚风险评价表评价文献质量;运用 RevMan 5.4 进行 Meta 分析,并绘制漏斗图;依据肥胖及代谢综合征(MS)定义、地域、炎症因子的具体类型等方面进行亚组分析。结果 共纳入12个国家的21项横断面研究,共23 308例研究对象,其中MHO者5 842例,代谢健康非肥胖(MHNO)者17 466例。Meta分析结果显示:白细胞计数(WBCC)(95%CI:0.02～0.18,P=0.01)、C反应蛋白(CRP)(95%CI:0.53～0.82,P<0.00001)、脂联素(APN)(95%CI:-1.43～-0.43,P=0.0003)、瘦素(LEP)(95%CI:1.39～0.43,P<0.00001)、白细胞介素(IL)-6(95%CI:0.13～1.29,P=0.02)均与成人MHO呈现相关性;各亚组分析提示,超敏C反应蛋白(hs-CRP)较CRP在两组人群中差异更显著(SMD=0.73,95%CI:0.59～0.88);在TNF-α与IL-6组中,BMI≥25 kg/m2较30 kg/m2作为肥胖诊断标准在两组人群差异更显著(SMD=1.14,95%CI:0.71～1.56)、(SMD=2.15,95%CI:1.65～2.64);北美洲的MHO较其他地域APN及LEP水平更高(SMD=-3.16,95%CI:-4.19～-2.13)、(SMD=8.46,95%CI:6.25,10.67)。本研究漏斗图分布对称性较好,提示无明显发表偏倚。结论 成人MHO与炎症因子中的WBCC、CRP、APN、LEP、IL-6具有一定相关性,针对肥胖人群血清炎症因子的检测对于肥胖相关疾病的早期预警有重要意义。
Abstract
Objective To systematically evaluate the association between adult metabolically healthy obesity (MHO) and various inflammatory factors, and to provide a basis for the early serological warning of obesity inflammation. Methods Cross-sectional studies on the association between MHO and inflammatory factors from CNKI, Wanfang, VIP, CBM , PubMed, Web of Science , Embase and Cochrane Library were retrieved, with the publication time limit set from inception to August 3, 2024. The quality of the literature was evaluated using the bias risk assessment form from AHRQ. Meta analysis was performed using RevMan 5.4 and a funnel plot was drawn. Subgroup analysis was conducted based on such aspects as the definitions of obesity and MS definitions (MS), regions and specific types of inflammatory factors. Results A total of 21 cross-sectional studies from 12 countries were included, involving 23308 research subjects, including 5842 MHO people and 17466 MHNO people. Meta-analysis results showed that white blood cell count (WBCC) (95%CI:0. 02~ 0. 18,P=0. 01), c-reactive protein (CRP) (95%CI:0. 53~0. 82,P<0. 00001), adiponectin (APN) (95%CI:-1 . 43 ~ -0. 43,P=0. 0003), leptin (LEP) ( 9 5%C I:1. 39 ~ 0 . 43, P< 0. 00001 ), and interleukin (IL) -6 (95%CI :0.1 3~1. 29,P=0. 02 ) were all correlated with adult metabolic health obesity. Analysis of each subgroup suggested that hypersensitive C-reactive protein (ha-CRP) showed a more significant difference than CRP in the two groups of people (SMD=0. 73, 95 %CI:0. 59 ~ 0. 88) . In the TNF-α and IL-6 groups, BMI≥25 kg/m2 was more significant than 30 kg/m2 as the diagnostic criterion for obesity between the two groups(SMD=1. 14,95%CI:0. 71~ 1. 56),(SMD = 2. 15,95 %C I:1. 6 5~ 2 . 64) . MHO people in North America had higher levels of APN and LEP than those in other regions( SMD =- 3. 16, 95%CI:-4.19~ -2. 13 ),( SMD = 8. 46 ,9 5% CI:6. 25 ,10. 67 ); The distribution symmetry of the funnel plot in this study was relatively good, indicating no significant publication bias. Conclusions Adult MHO is significantly correlated with inflammatory factors such as WBCC, CRP, APN, LEP, and IL-6. The detection of serum inflammatory factors in obese individuals is of great significance for early warning of obesity-related diseases.
关键词
代谢健康型肥胖 /
炎症因子 /
早期预警 /
Meta分析
Key words
metabolically healthy obesity /
inflammatory factor /
early warning /
meta analysis
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参考文献
[1] Welsh A, Hammad M, Piña I L, et al. Obesity and cardiovascular health [J]. Eur J Prev Cardiol, 2024, 31(8): 1026-1035.
[2] Novelli G, Cassadonte C, Sbraccia P, et al. Genetics: a starting point for the prevention and the treatment of obesity [J]. Nutrients, 2023, 15(12): 2782.
[3] Petersen M C, Smith G I, Palacios H H, et al. Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity [J]. Cell Metab, 2024, 36(4): 745-761.
[4] Blüher M. Metabolically healthy obesity [J]. Endocr Rev, 2020, 41(3): bnaa004.
[5] Tsatsoulis A, Paschou S A. Metabolically healthy obesity: criteria, epidemiology, controversies, and consequences [J]. Curr Obes Rep, 2020, 9(2): 109-120.
[6] Gao M, Lv J, Yu C, et al. Metabolically healthy obesity, transition to unhealthy metabolic status, and vascular disease in Chinese adults: a cohort study [J]. PLoS Med, 2020, 17(10): e1003351.
[7] Lin L, Zhang J, Jiang L, et al. Transition of metabolic phenotypes and risk of subclinical atherosclerosis according to BMI: a prospective study [J]. Diabetologia, 2020, 63(7): 1312-1323.
[8] Schulze M B, Stefan N. Metabolically healthy obesity: from epidemiology?and mechanisms to clinical implications [J].Nat Rev Endocrinol, 2024, 20(11): 633-646.
[9] 李纪新, 邱林杰, 任 燕,等.肥胖慢性炎症中医药治疗的潜在靶点: 巨噬细胞极化 [J]. 中国中药杂志, 2023, 48(19): 5113-5121.
[10] Li X, Ren Y, Chang K, et al. Adipose tissue macrophages as potential targets for obesity and metabolic diseases [J]. Front Immunol, 2023, 14: 1153915.
[11] Su Z, Efremov L, Mikolajczyk R. Differences in the levels of inflammatory markers between metabolically healthy obese and other obesity phenotypes in adults: a systematic review and meta-analysis [J]. Nutr Metab Cardiovasc Dis, 2024, 34(2): 251-269.
[12] Blüher S, Schwarz P. Metabolically healthy obesity from childhood to adulthood - does weight status alone matter? [J]. Metabolism, 2014, 63(9): 1084-1092.
[13] Spoto B, Di Betta E, Pizzini P, et al. Inflammation biomarkers and inflammatory genes expression in metabolically healthy obese patients [J]. Nutr Metab Cardiovasc Dis, 2023, 33(3): 584-591.
[14] 曾宪涛, 刘 慧, 陈 曦, 等. Meta分析系列之四: 观察性研究的质量评价工具 [J]. 中国循证心血管医学杂志, 2012, 4(4): 297-299.
[15] 柳 宁, 庄思琪, 付瑶阳, 等. 白介素-5和白介素-13血清水平与不同肥胖表型的关联分析 [J]. 实用预防医学, 2020, 27(10): 1176-1181.
[16] 韦 悦. 不同代谢状态肥胖表型与糖尿病发生风险关联及不同代谢状态细胞因子水平差异[D]. 华中科技大学, 2021.
[17] 孙 燕, 王佑民, 周换丽. 脂联素分子构成在代谢正常肥胖人群中的变化 [J]. 安徽医科大学学报, 2016, 51(2): 250-254.
[18] Gökçay Canpolat A, Demir Ö, Sahin M, et al. The missing link between inflammation and arterial stiffness among different metabolic phenotypes [J]. Int J Clin Pract, 2021, 75(11): e14727.
[19] Wang X L, Chang X Y, Tang X X, et al. Peripheral invariant natural killer T cell deficiency in metabolically unhealthy but normal weight versus metabolically healthy but obese individuals [J]. J Int Med Res, 2016, 44(6): 1272-1282.
[20] Ferreira F G, Reitz L K, Valmorbida A, et al. Metabolically unhealthy and overweight phenotypes are associated with increased levels of inflammatory cytokines: a population-based study [J]. Nutrition, 2022, 96: 111590.
[21] Liao C, Gao W, Cao W, et al. Associations of metabolic/obesity phenotypes with insulin resistance and c-reactive protein: results from the CNTR study [J]. Diabetes Metab Syndr Obes, 2021, 14: 1141-1151.
[22] Christou K A, Christou G A, Karamoutsios A, et al. Metabolically healthy obesity is characterized by a proinflammatory phenotype of circulating monocyte subsets [J]. Metab Syndr Relat Disord, 2019, 17(5): 259-265.
[23] Iglesias Molli A E, Penas Steinhardt A, López A P, et al. Metabolically healthy obese individuals present similar chronic inflammation level but less insulin-resistance than obese individuals with metabolic syndrome [J]. PLoS One, 2017, 12(12): e0190528.
[24] Hosseini S A, Aghamohammadi V, Ashtary-larky D, et al. Are young Iranian women with metabolically healthy obesity at increased risk of CVD incidence? [J]. J Vasc Bras, 2020, 19: e20190106.
[25] Shulkina S G, Smirnova E N, Yudin M I, et al. Adipocytokines in metabolically healthy obesity [J]. Ital J Med,2019, 13(3): 169-175.
[26] Lejawa M, Osadnik K, Czuba Z, et al. Association of metabolically healthy and unhealthy obesity phenotype with markers related to obesity, diabetes among young, healthy adult men. Analysis of magnetic study [J]. Life (Basel), 2021, 11(12): 1350.
[27] Petersen M C, Smith G I, Palacios H H, et al. Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity [J]. Cell Metab, 2024, 36(4): 745-761. e5.
[28] Aisike G, Kuerbanjiang M, Muheyati D, et al. Correlation analysis of obesity phenotypes with leptin and adiponectin [J]. Sci Rep, 2023, 13(1): 17718.
[29] Shaharyar S, Roberson L L, Jamal O, et al. Obesity and metabolic phenotypes (metabolically healthy and unhealthy variants) are significantly associated with prevalence of elevated C-reactive protein and hepatic steatosis in a large healthy Brazilian population [J]. J Obes, 2015, 2015: 178526.
[30] Jung C H, Lee M J, Hwang J Y, et al. Association of metabolically healthy obesity with subclinical coronary atherosclerosis in a Korean population [J]. Obesity (Silver Spring), 2014, 22(12): 2613-2620.
[31] Kang Y M, Jung C H, Cho Y K, et al. Visceral adiposity index predicts the conversion of metabolically healthy obesity to an unhealthy phenotype [J]. PLoS One, 2017, 12(6): e0179635.
[32] Oliveira M A, Faerstein E, Koury J C, et al. Vitamin D is directly associated with favorable glycemic, lipid, and inflammatory profiles in individuals with at least one component of metabolic syndrome irrespective of total adiposity: Pró-Saúde Study, Brazil [J]. Nutr Res, 2021, 96: 1-8.
[33] Fu J, Wang Q, Zhang L, et al. Serum bilirubin level is increased in metabolically healthy obesity [J]. Front Endocrinol (Lausanne), 2022, 12: 792795.
[34] Phillips C M, Perry I J. Does inflammation determine metabolic health status in obese and nonobese adults? [J]. J Clin Endocrinol Metab, 2013, 98(10): E1610-E1619.
[35] Masih D, Tripathi J K, Rakhra G, et al. Deciphering biochemical and molecular signatures associated with obesity in context of metabolic health [J]. Genes (Basel), 2021, 12(2): 290.
[36] Kawai T, Autieri M V, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity [J]. Am J Physiol Cell Physiol, 2021, 320(3): C375-C391.
[37] Wang T, He C. Pro-inflammatory cytokines: the link between obesity and osteoarthritis [J]. Cytokine Growth Factor Rev,2018, 44: 38-50.
[38] Smith G I, Mittendorfer B, Klein S. Metabolically healthy obesity: facts and fantasies [J]. J Clin Invest, 2019, 129(10): 3978-3989.
[39] Takaya J, Tanabe Y, Nomura N, et al. Platelet and white blood cell counts correlate with leptin and body mass index in Japanese adolescents [J]. Clin Pediatr Endocrinol, 2024, 33(4): 207-213.
[40] Li Z, Jin L, Xia L, et al. Body mass index, c-reactive protein, and pancreatic cancer: a mendelian randomization analysis to investigate causal pathways [J]. Front Oncol, 2023, 13: 1042567.
[41] Patsalos O, Dalton B, Himmerich H. Effects of IL-6 signaling pathway inhibition on weight and BMI: a systematic review and meta-analysis [J]. Int J Mol Sci, 2020, 21(17): 6290.
[42] Slattery M L, Wolff R K. Leptin and colorectal cancer: an undefined link [J]. Nat Clin Pract Gastroenterol Hepatol, 2007, 4(3): 118-119.
[43] Bakinowska E, Krompiewski M, Boboryko D, et al. The role of inflammatory mediators in the pathogenesis of obesity [J]. Nutrients, 2024, 16(17): 2822.
[44] Alzamil H. Elevated serum TNF-α is related to obesity in type 2 diabetes mellitus and is associated with glycemic control and insulin resistance [J]. J Obes, 2020, 2020: 5076858.
[45] Bian A L, Hu H Y, Rong Y D, et al. A study on relationship between elderly sarcopenia and inflammatory factors IL-6 and TNF-α [J]. Eur J Med Res, 2017, 22(1): 25.
[46] Pearson T A, Mensah G A, Alexander R W, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the centers for disease control and prevention and the american heart association [J]. Circulation,2003, 107(3): 499-511.
[47] Shivappa N, Hébert J R, Rietzschel E R, et al. Associations between dietary inflammatory index and inflammatory markers in the Asklepios Study [J]. Br J Nutr, 2015, 113(4): 665-671.
[48] Expert panel on detection E. Executive summary of the third reportof the national cholesterol education program (NCEP) expert panelon detection,evaluation, and treatment of high blood cholesterol inadults (adult treatment panel III) [J]. JAMA, 2001, 285(19): 2486-2497.
[49] Hinnouho G M, Czernichow S, Dugravot A, et al. Metabolically healthy obesity and the risk of cardiovascular disease and type 2 diabetes: the Whitehall II cohort study [J]. Eur Heart J, 2015, 36(9): 551-559.
[50] Su Z, Efremov L, Mikolajczyk R. Differences in the levels of inflammatory markers between metabolically healthy obese and other obesity phenotypes in adults: a systematic review and meta-analysis [J]. Nutr Metab Cardiovasc Dis, 2024, 34(2): 251-269.
[51] 国家卫生健康委办公厅. 国家卫生健康委办公厅关于印发肥胖症诊疗指南(2024年版)的通知[EB/OL].(2024-10-12)[2024-10-29]. https://www.gov.cn/zhengce/zhengceku/202410/content_6981734.htm.
基金
中国中医科学院西苑医院具有知识产权的医疗机构制剂和中药新药的研究与转化专项(XYZX0301-16); 北京中医药薪火传承“3+3”工程项目(2023-SZ-A-5);中国中医科学院科技创新工程(CI2021A03005)
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