Meta-analysis on the association between adult metabolically healthy obesity and inflammatory factors
WU Zijing1,2, LI Jixin2, QIU Linjie2, REN Yan2, ZOU Chacha 1,2, LI Meijie1,2, LI Wenjie2, ZHANG Jin2
1. Beijing University of Traditional Chinese Medicine, Beijing 100029, China; 2. Physical Examination Department /Disease Prevent Center, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
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.
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.
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.
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.
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.