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Li Z, Yao Z, Liu Q. The association between white blood cell counts and metabolic health obesity among US adults. Front Nutr 2025; 12:1458764. [PMID: 39895838 PMCID: PMC11784339 DOI: 10.3389/fnut.2025.1458764] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 01/03/2025] [Indexed: 02/04/2025] Open
Abstract
Background The correlation between white cell count and metabolically healthy obesity (MHO) remains elusive among obese American adults. This study endeavors to elucidate this association. Methods This study enrolled 6,580 obese patients from the National Health and Nutrition Examination Survey (NHANES). Obesity phenotypes were defined by presence/absence of metabolic syndrome components. Weighted multivariate logistic regression analyses were used to assess the association between white cell count and MHO occurrence. Restricted cubic spline analysis characterized dose-response relationships, and stratified analyses explored these relationships across sociodemographic and lifestyle factors. Results In this study, MHO prevalence is 11.9% among obese adults. The risk of MHO was inversely correlated with WBC [OR (95%): 0.81 (0.76, 0.86), p < 0.001], lymphocytes [OR (95%): 0.56 (0.47, 0.68), p < 0.001], monocytes [OR (95%): 0.41 (0.22, 0.75), p = 0.004], and neutrophils count [OR (95%): 0.82 (0.76, 0.88), p < 0.001]. WBC and neutrophils showed L-shaped associations, while lymphocytes, monocytes, and RBCs had linear patterns. Furthermore, stratified analyses demonstrated blood cell counts consistently predicted MHO risk across subgroups. Conclusion In this study, we provide novel insights into the association between blood cell count and the presence of MHO among obese individuals. Blood cell count is an accessible biomarker for dynamically tracking the presence of MHO.
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Affiliation(s)
- Zhanbin Li
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China
- Key Laboratory of Metabolism and Gastrointestinal Tumor, the First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Zhenyu Yao
- Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China
- Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China
| | - Qiaoran Liu
- Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, China
- Key Laboratory of Metabolism and Gastrointestinal Tumor, the First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
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Baek SU, Yoon JH. Systemic Inflammation Across Metabolic Obesity Phenotypes: A Cross-Sectional Study of Korean Adults Using High-Sensitivity C-Reactive Protein as a Biomarker. Int J Mol Sci 2024; 25:11540. [PMID: 39519093 PMCID: PMC11547168 DOI: 10.3390/ijms252111540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 10/25/2024] [Accepted: 10/26/2024] [Indexed: 11/16/2024] Open
Abstract
Chronic systemic inflammation is a hallmark of obesity. This cross-sectional study aimed to investigate the association between metabolic obesity phenotypes and inflammatory markers in Korean adults (N = 21,112; mean age: 50.9 ± 16.6). Metabolic obesity phenotypes were categorized into metabolically healthy non-obesity (MHNO), metabolically unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO) based on body mass index and the presence of any metabolic abnormalities. High-sensitivity C-reactive protein (hs-CRP) levels were measured. Multiple linear regression was used to determine the association between obesity phenotypes and hs-CRP levels. In the male sample, compared to the MHNO type, the MUNO, MHO, and MUO types were associated with a 22.3% (95% confidence interval; CI: 14.7-30.3%), 15.8% (95% CI: 2.6-30.7%), and 12.5% (95% CI: 3.0-22.9%) increase in the hs-CRP levels, respectively. The association between metabolic obesity types and hs-CRP levels was stronger among the female sample; compared to the MHNO type, the MUNO, MHO, and MUO types were associated with a 30.2% (95% CI: 22.8-38.2%), 16.0% (95% CI: 6.5-26.4%), and 22.8% (95% CI: 13.6-32.8%) increase in the hs-CRP levels, respectively. Our findings indicate a varying profile of systemic inflammation across different metabolic obesity phenotypes.
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Affiliation(s)
- Seong-Uk Baek
- Graduate School, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jin-Ha Yoon
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
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Xiao L, Li Y, Hong C, Ma P, Zhu H, Cui H, Zou X, Wang J, Li R, He J, Liang S, Li Z, Zeng L, Liu L. Polygenic risk score of metabolic dysfunction-associated steatotic liver disease amplifies the health impact on severe liver disease and metabolism-related outcomes. J Transl Med 2024; 22:650. [PMID: 38997780 PMCID: PMC11241780 DOI: 10.1186/s12967-024-05478-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 07/03/2024] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes. METHODS Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes. RESULTS Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes. CONCLUSIONS High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.
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Affiliation(s)
- Lushan Xiao
- Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yan Li
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Chang Hong
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Pengcheng Ma
- Big Data Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Hongbo Zhu
- Department of Medical Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China
| | - Hao Cui
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Xuejing Zou
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jiaren Wang
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Ruining Li
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Jingzhe He
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Shengxing Liang
- School of Public Health, Southern Medical University, Guangzhou, 510515, China
| | - Zeyang Li
- School of Health Management, Southern Medical University, Guangzhou, 510515, China
| | - Lin Zeng
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
| | - Li Liu
- Department of Health Management, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
- Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
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Mouton AJ, do Carmo JM, da Silva AA, Omoto ACM, Hall JE. Targeting immunometabolism during cardiorenal injury: roles of conventional and alternative macrophage metabolic fuels. Front Physiol 2023; 14:1139296. [PMID: 37234412 PMCID: PMC10208225 DOI: 10.3389/fphys.2023.1139296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 04/14/2023] [Indexed: 05/28/2023] Open
Abstract
Macrophages play critical roles in mediating and resolving tissue injury as well as tissue remodeling during cardiorenal disease. Altered immunometabolism, particularly macrophage metabolism, is a critical underlying mechanism of immune dysfunction and inflammation, particularly in individuals with underlying metabolic abnormalities. In this review, we discuss the critical roles of macrophages in cardiac and renal injury and disease. We also highlight the roles of macrophage metabolism and discuss metabolic abnormalities, such as obesity and diabetes, which may impair normal macrophage metabolism and thus predispose individuals to cardiorenal inflammation and injury. As the roles of macrophage glucose and fatty acid metabolism have been extensively discussed elsewhere, we focus on the roles of alternative fuels, such as lactate and ketones, which play underappreciated roles during cardiac and renal injury and heavily influence macrophage phenotypes.
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Affiliation(s)
- Alan J. Mouton
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States
- Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, United States
| | - Jussara M. do Carmo
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States
- Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, United States
| | - Alexandre A. da Silva
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States
- Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, United States
| | - Ana C. M. Omoto
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States
- Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, United States
| | - John E. Hall
- Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States
- Mississippi Center for Obesity Research, University of Mississippi Medical Center, Jackson, MS, United States
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Ray A, Bonorden MJL, Pandit R, Nkhata KJ, Bishayee A. Infections and immunity: associations with obesity and related metabolic disorders. J Pathol Transl Med 2023; 57:28-42. [PMID: 36647284 PMCID: PMC9846011 DOI: 10.4132/jptm.2022.11.14] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Accepted: 11/14/2022] [Indexed: 01/18/2023] Open
Abstract
About one-fourth of the global population is either overweight or obese, both of which increase the risk of insulin resistance, cardiovascular diseases, and infections. In obesity, both immune cells and adipocytes produce an excess of pro-inflammatory cytokines that may play a significant role in disease progression. In the recent coronavirus disease 2019 (COVID-19) pandemic, important pathological characteristics such as involvement of the renin-angiotensin-aldosterone system, endothelial injury, and pro-inflammatory cytokine release have been shown to be connected with obesity and associated sequelae such as insulin resistance/type 2 diabetes and hypertension. This pathological connection may explain the severity of COVID-19 in patients with metabolic disorders. Many studies have also reported an association between type 2 diabetes and persistent viral infections. Similarly, diabetes favors the growth of various microorganisms including protozoal pathogens as well as opportunistic bacteria and fungi. Furthermore, diabetes is a risk factor for a number of prion-like diseases. There is also an interesting relationship between helminths and type 2 diabetes; helminthiasis may reduce the pro-inflammatory state, but is also associated with type 2 diabetes or even neoplastic processes. Several studies have also documented altered circulating levels of neutrophils, lymphocytes, and monocytes in obesity, which likely modifies vaccine effectiveness. Timely monitoring of inflammatory markers (e.g., C-reactive protein) and energy homeostasis markers (e.g., leptin) could be helpful in preventing many obesity-related diseases.
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Affiliation(s)
- Amitabha Ray
- College of Medical Science, Alderson Broaddus University, Philippi, WV, USA,Corresponding Author: Amitabha Ray, MD, PhD, College of Medical Science, Alderson Broaddus University, 101 College Hill Drive, Philippi, WV 26416, USA Tel: +1-304-457-6587, Fax: +1-304-457-6308, E-mail:
| | | | - Rajashree Pandit
- Division of Medical & Behavioral Health, Pueblo Community College, Pueblo, CO, USA
| | | | - Anupam Bishayee
- Lake Erie College of Osteopathic Medicine, Bradenton, FL, USA
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Gutierrez-Huerta CA, Turner BS, Claudel SE, Farmer N, Islam R, Mitchell VM, Collins BS, Baumer Y, Remaley AT, Powell-Wiley TM. LDL associates with pro-inflammatory monocyte subset differentiation and increases in chemokine receptor profile expression in African Americans. Int J Cardiol 2022; 358:88-93. [PMID: 35436557 PMCID: PMC9120048 DOI: 10.1016/j.ijcard.2022.04.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 04/06/2022] [Accepted: 04/12/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND In the United States, African Americans (AAs) have greater risk for Class III obesity and cardiovascular disease (CVD). Previous reports suggest that AAs have a different immune cell profile when compared to Caucasians. METHODS The immune cell profile of AAs was characterized by flow cytometry using two experimental setups: ex vivo (N = 40) and in vitro (N = 10). For ex vivo experiments, PBMC were treated with participant serum to understand how lipid contents may contribute to monocyte phenotypic differences. For in vitro experiments, monocytes were low-density lipoprotein (LDL)- or vehicle-treated for four hours and subsequently analyzed by flow cytometry and RT-qPCR. RESULTS When PBMCs were treated with participant sera, subsequent multivariable regression analysis revealed that serum triglycerides and LDL levels were associated with monocyte subset differences. In vitro LDL treatment of monocytes induced a phenotypic switch in monocytes away from classical monocytes accompanied by subset-specific chemokine receptor CCR2 and CCR5 expression changes. These observed changes are partially translation-dependent as determined by co-incubation with cycloheximide. CONCLUSIONS LDL treatment of monocytes induces a change in monocyte subsets and increases CCR2/CCR5 expression in a subset-specific manner. Understanding the molecular mechanisms could prove to have CVD-related therapeutic benefits, especially in high-risk populations with hyperlipidemia and increased risk for CVD.
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Affiliation(s)
- Cristhian A Gutierrez-Huerta
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Briana S Turner
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Sophie E Claudel
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Nicole Farmer
- Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
| | - Rafique Islam
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Valerie M Mitchell
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Billy S Collins
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Yvonne Baumer
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Alan T Remaley
- Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Tiffany M Powell-Wiley
- Social Determinants of Obesity and Cardiovascular Risk Laboratory, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA; Intramural Research Program, National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD, USA.
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Jin JL, Zhang HW, Liu HH, Zhu CG, Guo YL, Wu NQ, Xu RX, Dong Q, Li JJ. Lipoprotein(a) and Cardiovascular Outcomes in Patients With Coronary Artery Disease and Different Metabolic Phenotypes. Front Cardiovasc Med 2022; 9:870341. [PMID: 35669468 PMCID: PMC9163309 DOI: 10.3389/fcvm.2022.870341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 04/20/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The positive relationship between metabolic healthy obesity (MHO) and cardiovascular risk has been under debate in recent years. Previously, strong evidence supported the causal role of increased plasma lipoprotein(a) [Lp(a)] levels in cardiovascular disease (CVD). The current study aimed to investigate the different associations of Lp(a) and cardiovascular events (CVEs) in patients with coronary artery disease (CAD) and different metabolic phenotypes. METHODS A total of 5,089 patients who were angiography-proven CAD were consecutively included and followed up for CVEs. Obesity was defined as a body mass index (BMI) ≥25 kg/m2 according to Asia-specific BMI criteria. Patients were divided into four groups according to metabolic phenotypes, namely metabolically healthy/unhealthy non-obese and metabolically healthy/unhealthy obese [metabolically healthy non-obese (MHN), MHO, metabolically unhealthy non-obese (MUN), and metabolically unhealthy obesity (MUO)]. Comparisons of CAD severity and outcomes were performed among four groups. Cox regression analyses and cubic spline models were used to examine the relationship between Lp(a) and CVEs in patients with different metabolic phenotypes. RESULTS During a median of 7.5 years' follow-up, 540 (10.6%) CVEs occurred. MUN and MUO populations had more severe coronary stenosis than MHN ones, while no significant difference in the Gensini score (GS) was observed between MHN and MHO. Patients with MUN and MUO presented a higher risk of CVEs than patients with MHN (hazard ratio [HR]: 1.414, 95% CI: 1.024-1.953-1.556 and HR: 1.747, 95% CI: 1.295-1.363, p < 0.05). In subgroup analysis, restricted cubic spline models showed that there was no association between Lp(a) and CVEs in patients in MHN and MHO, while the MUN and MUO groups presented increasing associations between Lp(a) and CVEs and such association was stronger in the MUO group. In Cox regression analysis, Lp(a) >50 mg/dl was associated with a 2.032- and 2.206-fold higher risk of subsequent CVEs in the MUO and MUN subgroups, respectively. CONCLUSION Among patients with angiography-proven stable CAD, Lp(a) had a more significant prognostic value in both MUO and MUN individuals regardless of obesity, suggesting the importance of screening for cardiovascular risk with Lp(a) in metabolically unhealthy patients.
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Affiliation(s)
- Jing-Lu Jin
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
- Department of Endocrinology, Genetics, and Metabolism, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China
| | - Hui-Wen Zhang
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Hui-Hui Liu
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Cheng-Gang Zhu
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Yuan-Lin Guo
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Na-Qiong Wu
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Rui-Xia Xu
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Qian Dong
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
| | - Jian-Jun Li
- Key Laboratory of Cardiovascular Disease, Cardiometabolic Center, National Center for Cardiovascular Diseases, Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
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Rees A, Richards O, Allen-Kormylo A, Jones N, Thornton CA. Maternal body mass index is associated with an altered immunological profile at 28 weeks of gestation. Clin Exp Immunol 2022; 208:114-128. [PMID: 35304898 PMCID: PMC9113395 DOI: 10.1093/cei/uxac023] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 01/31/2022] [Accepted: 03/18/2022] [Indexed: 01/12/2023] Open
Abstract
Healthy pregnancy is accompanied by various immunological and metabolic adaptations. Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia, and gestational diabetes mellitus (GDM), while posing a risk to the neonate. There is a lack of knowledge surrounding obesity and the maternal immune system. The objective of this study was to consider if immunological changes in pregnancy are influenced by maternal obesity. Peripheral blood was collected from fasted GDM-negative pregnant women at 26-28 weeks of gestation. Analysis was done using immunoassay, flow cytometry, bioenergetics analysis, and cell culture. The plasma profile was significantly altered with increasing BMI, specifically leptin (r = 0.7635), MCP-1 (r = 0.3024), and IL-6 (r = 0.4985). Circulating leukocyte populations were also affected with changes in the relative abundance of intermediate monocytes (r = -0.2394), CD4:CD8 T-cell ratios (r = 0.2789), and NKT cells (r = -0.2842). Monocytes analysed in more detail revealed elevated CCR2 expression and decreased mitochondrial content with increased BMI. However, LPS-stimulated cytokine production and bioenergetic profile of PBMCs were not affected by maternal BMI. The Th profile skews towards Th17 with increasing BMI; Th2 (r = -0.3202) and Th9 (r = -0.3205) cells were diminished in maternal obesity, and CytoStim™-stimulation exacerbates IL-6 (r = 0.4166), IL-17A (r = 0.2753), IL-17F (r = 0.2973), and IL-22 (r = 0.2257) production with BMI, while decreasing IL-4 (r = -0.2806). Maternal obesity during pregnancy creates an inflammatory microenvironment. Successful pregnancy requires Th2-biased responses yet increasing maternal BMI favours a Th17 response that could be detrimental to pregnancy. Further research should investigate key populations of cells identified here to further understand the immunological challenges that beset pregnant women with obesity.
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Affiliation(s)
- April Rees
- Institute of Life Science, Swansea University Medical School, Swansea, UK
| | - Oliver Richards
- Institute of Life Science, Swansea University Medical School, Swansea, UK
| | - Anastasia Allen-Kormylo
- Maternity and Child Health, Singleton Hospital, Swansea Bay University Health Board, Swansea, UK
| | - Nicholas Jones
- Institute of Life Science, Swansea University Medical School, Swansea, UK
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Sanoudou D, Hill MA, Belanger MJ, Arao K, Mantzoros CS. Editorial: Obesity, metabolic phenotypes and COVID-19. Metabolism 2022; 128:155121. [PMID: 35026232 PMCID: PMC8743503 DOI: 10.1016/j.metabol.2021.155121] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 12/27/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023]
Affiliation(s)
- Despina Sanoudou
- 4th Department of Internal Medicine, Clinical Genomics and Pharmacogenomics Unit, 'Attikon' Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Molecular Biology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
| | - Michael A Hill
- Dalton Cardiovascular Research Center and Department of Medical Pharmacology and Physiology, School of Medicine, University of Missouri, Columbia, 65211, MO, USA.
| | | | - Kevin Arao
- Department of Medicine, Boston VA Healthcare System and Boston University School of Medicine, Boston, MA 02115, USA
| | - Christos S Mantzoros
- Department of Medicine, Boston VA Healthcare System and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Wu Q, Xia MF, Gao X. Metabolically healthy obesity: Is it really healthy for type 2 diabetes mellitus? World J Diabetes 2022; 13:70-84. [PMID: 35211245 PMCID: PMC8855137 DOI: 10.4239/wjd.v13.i2.70] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 04/27/2021] [Accepted: 01/20/2022] [Indexed: 02/06/2023] Open
Abstract
Metabolically healthy obese (MHO) individuals are reported to have a lower risk of developing cardiovascular diseases in comparison with individuals with metabolic syndrome. However, the association between MHO and type 2 diabetes (T2DM) is still controversial. Some studies indicated that MHO is a favorable phenotype for T2DM, but more studies showed that MHO individuals have an increased risk of developing T2DM compared with metabolically healthy normal-weight individuals, especially among those who would acquire metabolically unhealthy obesity. This has been supported by finding insulin resistance and low-grade inflammatory responses in MHO individuals with a tendency for impaired beta-cell dysfunction. Studies also showed that liver fat accumulation increased the risk of incidence of T2DM in MHO. Here, we reviewed current literature on the relationship between MHO and T2DM, discussed the determinants for the development of diabetes in MHO, and summarized the measures for the prevention of T2DM in MHO.
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Affiliation(s)
- Qi Wu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai 200032, China
| | - Ming-Feng Xia
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai 200032, China
| | - Xin Gao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
- Fudan Institute for Metabolic Disease, Fudan University, Shanghai 200032, China
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Christou GA. Not only the status of body weight and metabolic health matters for cardiovascular events, but also the temporal changes. Eur J Prev Cardiol 2022; 28:e25-e27. [PMID: 32588657 DOI: 10.1177/2047487320937489] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Georgios A Christou
- Laboratory of Sports Medicine, Sports Medicine Division, Aristotle University of Thessaloniki, Thessaloniki, Greece
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12
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Gálvez I, Navarro MC, Martín-Cordero L, Otero E, Hinchado MD, Ortega E. The Influence of Obesity and Weight Loss on the Bioregulation of Innate/Inflammatory Responses: Macrophages and Immunometabolism. Nutrients 2022; 14:nu14030612. [PMID: 35276970 PMCID: PMC8840693 DOI: 10.3390/nu14030612] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 01/24/2022] [Accepted: 01/27/2022] [Indexed: 12/12/2022] Open
Abstract
Obesity is characterized by low-grade inflammation and more susceptibility to infection, particularly viral infections, as clearly demonstrated in COVID-19. In this context, immunometabolism and metabolic flexibility of macrophages play an important role. Since inflammation is an inherent part of the innate response, strategies for decreasing the inflammatory response must avoid immunocompromise the innate defenses against pathogen challenges. The concept “bioregulation of inflammatory/innate responses” was coined in the context of the effects of exercise on these responses, implying a reduction in excessive inflammatory response, together with the preservation or stimulation of the innate response, with good transitions between pro- and anti-inflammatory macrophages adapted to each individual’s inflammatory set-point in inflammatory diseases, particularly in obesity. The question now is whether these responses can be obtained in the context of weight loss by dietary interventions (low-fat diet or abandonment of the high-fat diet) in the absence of exercise, which can be especially relevant for obese individuals with difficulties exercising such as those suffering from persistent COVID-19. Results from recent studies are controversial and do not point to a clear anti-inflammatory effect of these dietary interventions, particularly in the adipose tissue. Further research focusing on the innate response is also necessary.
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Affiliation(s)
- Isabel Gálvez
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Nursing Department, Faculty of Medicine and Health Sciences, University of Extremadura, 06071 Badajoz, Spain
| | - María Carmen Navarro
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071 Badajoz, Spain
| | - Leticia Martín-Cordero
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Nursing Department, University Center of Plasencia, University of Extremadura, 10600 Plasencia, Spain
| | - Eduardo Otero
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071 Badajoz, Spain
| | - María Dolores Hinchado
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071 Badajoz, Spain
| | - Eduardo Ortega
- Immunophyisiology Research Group, Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 06071 Badajoz, Spain; (I.G.); (M.C.N.); (L.M.-C.); (E.O.); (M.D.H.)
- Immunophysiology Research Group, Physiology Department, Faculty of Sciences, University of Extremadura, 06071 Badajoz, Spain
- Correspondence: ; Tel.: +34-924-289-300
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13
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Serbis A, Giapros V, Paschou SA, Siomou E. Children with metabolically healthy obesity have a worse metabolic profile compared to normal-weight peers: a cross-sectional study. Endocrine 2021; 73:580-587. [PMID: 34023981 DOI: 10.1007/s12020-021-02762-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/10/2021] [Indexed: 12/25/2022]
Abstract
PURPOSE A phenotype of metabolically healthy obesity (MHO) has been described in youth with obesity, but data are still scarce in this age group. The aim of the current study was to describe and compare clinical and laboratory parameters related to obesity among three different groups of youth, namely youth with normal weight (NW), with MHO, and with metabolically unhealthy obesity (MUO). METHODS One hundred and three youngsters with obesity were divided according to 2018 consensus-based criteria into those with MHO [n = 49, age (±SD): 10.9 ± 2.9 years] and those with MUO [n = 54, 11.5 ± 2.7 years] and were compared to age-, sex- and Tanner-matched NW [n = 69, 11.3 ± 2.9 years]. Several obesity-related parameters were investigated for all three groups of children. Comparisons were made by analysis of variance (ANOVA) followed by the Fisher's PLSD test. RESULTS Youth with MHO had lower systolic (p < 0.001) and diastolic (p < 0.01) blood pressure z-score and triglycerides (p < 0.01), but higher HDL-C (p < 0.001), total cholesterol (p < 0.05), and apo-A1 (p < 0.05) compared to those with MUO. Compared to controls, both children with MHO and MUO showed higher fasting insulin (p < 0.05), HOMA-IR (p < 0.05), and QUICKI (p < 0.001). Similarly, both groups had higher hsCRP, fibrinogen, uric acid, and leptin compared to controls (for all, p < 0.001), while their adiponectin was lower (p < 0.05). Visfatin was higher in children with MUO compared to controls (p < 0.01), and it showed a trend to be lower in children with MHO compared to those with MUO (p = 0.1). CONCLUSION This study provides evidence that children identified as having MHO by the consensus-based criteria had better metabolic profiles than youth with MUO, but worse than NW. Further research is needed in pediatric populations both regarding MHO criteria and the nature of the MHO phenotype per se.
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Affiliation(s)
- Anastasios Serbis
- Child Health Department, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece.
| | - Vasilieios Giapros
- Child Health Department, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Stavroula A Paschou
- Division of Endocrinology, Diabetes and Metabolism, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Ekaterini Siomou
- Child Health Department, School of Health Sciences, Faculty of Medicine, University of Ioannina, Ioannina, Greece
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14
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Alexaki VI. The Impact of Obesity on Microglial Function: Immune, Metabolic and Endocrine Perspectives. Cells 2021; 10:cells10071584. [PMID: 34201844 PMCID: PMC8307603 DOI: 10.3390/cells10071584] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 06/18/2021] [Accepted: 06/22/2021] [Indexed: 02/06/2023] Open
Abstract
Increased life expectancy in combination with modern life style and high prevalence of obesity are important risk factors for development of neurodegenerative diseases. Neuroinflammation is a feature of neurodegenerative diseases, and microglia, the innate immune cells of the brain, are central players in it. The present review discusses the effects of obesity, chronic peripheral inflammation and obesity-associated metabolic and endocrine perturbations, including insulin resistance, dyslipidemia and increased glucocorticoid levels, on microglial function.
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Affiliation(s)
- Vasileia Ismini Alexaki
- Institute for Clinical Chemistry and Laboratory Medicine, University Clinic Carl Gustav Carus, TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany
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15
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Zhang SS, Yang XJ, Ma QH, Xu Y, Chen X, Wang P, Pan CW. Leukocyte related parameters in older adults with metabolically healthy and unhealthy overweight or obesity. Sci Rep 2021; 11:4652. [PMID: 33633339 PMCID: PMC7907258 DOI: 10.1038/s41598-021-84367-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 01/27/2021] [Indexed: 11/18/2022] Open
Abstract
It remains unclear whether leukocyte-related parameters could be used as biomarkers to differentiate metabolically unhealthy overweight/obesity (MUO) from metabolically healthy overweight/obesity (MHO). We aimed to examine the differences in the distribution of leukocyte-related parameters between older adults with MHO and MUO and the correlations of leukocyte-related parameters with individual components of metabolic abnormality. In the Weitang Geriatric Diseases Study on older Chinese adults aged 60 years or above, 404 individuals with MHO and 480 with MUO contributed to the analysis. Overweight/obesity was defined as body mass index (BMI) of 25 kg/m2 or more. MHO and MUO were discriminated based on the Adult Treatment Panel III (ATP III) criteria. Leukocyte-related parameters were assessed using an automated hematology analyzer. All leukocyte-related parameters except monocytes were elevated in MUO group compared with MHO group (all P < 0.05). The prevalence of MUO increased by 24% with each 109/L increase of leukocytes after adjusting for confounders in the multiple-adjusted model (P < 0.01) and each unit elevation of other parameters except lymphocytes and monocytes were significantly associated with the presence of MUO (all P < 0.01). Trend tests revealed a linear trend for the association between MUO and all the leukocyte-related parameters (all P for trend < 0.05). Significant interactions between leukocyte-related parameters and sex on the presence of MUO were observed (all P value for interaction < 0.05). Higher leukocyte-related parameters were found in patients with MUO than those with MHO and were associated with higher prevalence of MUO which seems to be sex-dependent. Further studies are needed to see whether these parameters could be used as biomarkers for the screening or diagnosis for MUO in clinical or public health practice.
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Affiliation(s)
- Shan-Shan Zhang
- School of Public Health, Medical College of Soochow University, 199 Ren Ai Road, Suzhou, 215123, China
| | - Xue-Jiao Yang
- School of Public Health, Medical College of Soochow University, 199 Ren Ai Road, Suzhou, 215123, China
| | - Qing-Hua Ma
- The 3rd People's Hospital of Xiangcheng District, Suzhou, 215134, China
| | - Yong Xu
- School of Public Health, Medical College of Soochow University, 199 Ren Ai Road, Suzhou, 215123, China
| | - Xing Chen
- Department of Children Health Care, Affiliated Suzhou Hospital of Nanjing Medical University, No.26, Dao Qian Road, Suzhou, 215000, China.
| | - Pei Wang
- Department of Health Economics, School of Public Health,, Fudan University, 130 Dong An Road, Shanghai, 200032, China.
- Key Lab of Health Technology Assessment, National Health Commission of the People's Republic of China (Fudan University), Shanghai, 200032, China.
| | - Chen-Wei Pan
- School of Public Health, Medical College of Soochow University, 199 Ren Ai Road, Suzhou, 215123, China.
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16
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Oh ES, Na M, Rogers CJ. The Association Between Monocyte Subsets and Cardiometabolic Disorders/Cardiovascular Disease: A Systematic Review and Meta-Analysis. Front Cardiovasc Med 2021; 8:640124. [PMID: 33681309 PMCID: PMC7925827 DOI: 10.3389/fcvm.2021.640124] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 01/27/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Monocyte subsets in humans, i.e., classical (CM), intermediate (IM), and non-classical monocytes (NCM), are thought to differentially contribute to the pathogenesis of atherosclerosis, the leading cause of cardiovascular disease (CVD). However, the association between monocyte subsets and cardiometabolic disorders and CVD is not well-understood. Thus, the aim of the current systematic review and meta-analysis was to evaluate recent findings from clinical studies that examined the association between the distribution of monocyte subsets in subjects with cardiometabolic disorders and CVD compared to healthy controls. Methods: Articles were systematically searched in CINAHL, PubMed and Cochrane Library. Articles were independently screened and selected by two reviewers. Studies that reported the percentage of each monocyte subset were included in the systematic review and meta-analysis. For the meta-analysis, a random-effects model was used to generate pooled standardized mean differences (SMD) between subjects with cardiometabolic disorders and healthy controls. Results: A total of 1,693 articles were screened and 27 studies were selected for qualitative analyses. Among them, six studies were included in the meta-analysis. In total, sample size ranged from 22 to 135 and mean or median age from 22 to 70 years old. We found studies that reported higher percentage and number of IM and/or NCM in subjects with cardiometabolic disorders (9 out of 13 studies) and in subjects with CVD (11 out of 15 studies) compared to healthy controls. In the meta-analysis, the percentage of CM was lower [SMD = −1.21; 95% CI (−1.92, −0.50); P = 0.0009; I2 = 91%] and the percentage of IM [SMD = 0.56; 95% CI (0.23, 0.88); P = 0.0008; I2 = 65%] and NCM [SMD = 1.39; 95% CI (0.59, 2.19); P = 0.0007; I2 = 93%] were higher in subjects with cardiometabolic disorders compared to healthy controls. Conclusions: Individuals with cardiometabolic disorders and CVD may have a higher percentage of IM and NCM than healthy controls. Future studies are needed to evaluate the cause and biological significance of this potential altered distribution of monocyte subsets.
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Affiliation(s)
- Ester S Oh
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, United States
| | - Muzi Na
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, United States
| | - Connie J Rogers
- Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, United States.,Center for Molecular Immunology and Infectious Disease, Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United States
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17
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Christou KA, Christou GA, Karamoutsios A, Vartholomatos G, Gartzonika K, Tsatsoulis A, Tigas S. The regulation of serum resistin levels in metabolically healthy and unhealthy obese individuals. Hormones (Athens) 2020; 19:523-529. [PMID: 32328905 DOI: 10.1007/s42000-020-00201-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Accepted: 04/07/2020] [Indexed: 12/23/2022]
Abstract
PURPOSE We have recently demonstrated that absolute counts of circulating proinflammatory monocytes were lower in obese patients without metabolic syndrome (MS) (metabolically healthy obese, MHO) compared with those with MS (metabolically unhealthy obese, MUO), but higher compared with healthy lean controls (MHL). We hypothesized that circulating resistin, a cytokine secreted by white blood cells (WBC), is involved in obesity-related low-grade inflammation. The aim of this study was to (a) determine serum resistin levels among MUO and MHO subjects and (b) investigate the role of circulating WBC subsets as potential determinants of resistin. METHODS Study participants were 58 obese (33 MUO, 25 MHO) and 25 MHL individuals. Serum levels of resistin, high-sensitivity C-reactive protein (hsCRP), and absolute counts of circulating WBC subpopulations were determined. Comparisons were sex- and age-adjusted. RESULTS Serum resistin levels in MHL were lower compared with those of obese (p = 0.041), but similar to those of MHO (p = 0.856) individuals. Both resistin (p = 0.005) and absolute neutrophil count (NeuA) (p = 0.025) were higher in MUO compared with MHO. The difference in resistin levels between obese and MHL individuals disappeared after adjustment for NeuA. Resistin correlated positively with absolute total monocyte count (p = 0.037) in MHL and with body mass index (BMI) (p = 0.023), hsCRP (p = 0.022), and NeuA (p = 0.044) in obese subjects. Resistin association with ΒΜΙ disappeared after adjustment for hsCRP, while association with hsCRP disappeared after further adjustment for NeuA. CONCLUSION Circulating resistin was higher in MUO compared with MHO. The increased secretion of resistin by the greater number of neutrophils in the former may have contributed to this regulation.
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Affiliation(s)
| | - Georgios A Christou
- Department of Endocrinology, University of Ioannina, 45110, Ioannina, Greece
| | - Achilleas Karamoutsios
- Laboratory of Haematology, Molecular Biology Unit, Ioannina University Hospital, Ioannina, Greece
| | - Georgios Vartholomatos
- Laboratory of Haematology, Molecular Biology Unit, Ioannina University Hospital, Ioannina, Greece
| | - Konstantina Gartzonika
- Laboratory of Immunology and Microbiology, School of Medicine, University of Ioannina, Ioannina, Greece
| | | | - Stelios Tigas
- Department of Endocrinology, University of Ioannina, 45110, Ioannina, Greece.
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18
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Hazeldine J, Lord JM. Immunesenescence: A Predisposing Risk Factor for the Development of COVID-19? Front Immunol 2020; 11:573662. [PMID: 33123152 PMCID: PMC7573102 DOI: 10.3389/fimmu.2020.573662] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 08/28/2020] [Indexed: 01/08/2023] Open
Abstract
Bearing a strong resemblance to the phenotypic and functional remodeling of the immune system that occurs during aging (termed immunesenescence), the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), is characterized by an expansion of inflammatory monocytes, functional exhaustion of lymphocytes, dysregulated myeloid responses and the presence of highly activated senescent T cells. Alongside advanced age, male gender and pre-existing co-morbidities [e.g., obesity and type 2 diabetes (T2D)] are emerging as significant risk factors for COVID-19. Interestingly, immunesenescence is more profound in males when compared to females, whilst accelerated aging of the immune system, termed premature immunesenescence, has been described in obese subjects and T2D patients. Thus, as three distinct demographic groups with an increased susceptibility to COVID-19 share a common immune profile, could immunesenescence be a generic contributory factor in the development of severe COVID-19? Here, by focussing on three key aspects of an immune response, namely pathogen recognition, elimination and resolution, we address this question by discussing how immunesenescence may weaken or exacerbate the immune response to SARS-CoV-2. We also highlight how aspects of immunesenescence could render potential COVID-19 treatments less effective in older adults and draw attention to certain therapeutic options, which by reversing or circumventing certain features of immunesenescence may prove to be beneficial for the treatment of groups at high risk of severe COVID-19.
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Affiliation(s)
- Jon Hazeldine
- Medical Research Council-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
| | - Janet M. Lord
- Medical Research Council-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
- National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospital Birmingham National Health Service Foundation Trust and University of Birmingham, Birmingham, United Kingdom
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19
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Maliakkal BJ. Pathogenesis of non-alcoholic fatty liver disease and implications on cardiovascular outcomes in liver transplantation. Transl Gastroenterol Hepatol 2020; 5:36. [PMID: 32632387 DOI: 10.21037/tgh.2019.12.02] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 11/05/2019] [Indexed: 12/15/2022] Open
Abstract
Along with the obesity epidemic there has been a major increase in non-alcoholic fatty liver disease (NAFLD) prevalence, paralleling a steady increase in cirrhosis of the liver and hepatocellular cancer (HCC) related to NAFLD. Currently, NAFLD (related HCC and cirrhosis) is the second most common cause for liver transplantation (LT) and it is projected to take the top spot in the next 3-5 years. Patients with NAFLD cirrhosis and HCC have a unique set of comorbidities which potentially increases their risk for cardiovascular disease (CVD) and mortality. However, a review of the published data in NAFLD patients who undergo LT, does not paint a clear picture. While CVD is the most common cause of non-graft related mortality over the long-term, the short and intermediate-term survival post LT in NAFLD cirrhosis appears to be on par with other etiologies when age and comorbidities are factored. The cardiovascular complications are increased in the immediate post-transplant period but there is a shift from ischemic complications to arrhythmias and heart failure (HF). NAFLD recurs in 80-100% patients and occurs de novo in about 50% after LT, potentially impacting their long-term morbidity and mortality. This review summarizes the available data on CVD in NAFLD patients before and after LT, explains what is currently known about the epidemiology and pathogenesis of CVD in NAFLD and posits strategies to improve wait-list and post-transplant survival.
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20
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Guo X, Li Z, Zhou Y, Yu S, Yang H, Sun G, Zheng L, Afzal J, Liu Y, Sun Y. The effects of transitions in metabolic health and obesity status on incident cardiovascular disease: Insights from a general Chinese population. Eur J Prev Cardiol 2020; 28:1250-1258. [PMID: 34551085 DOI: 10.1177/2047487320935550] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 05/29/2020] [Indexed: 12/29/2022]
Abstract
Abstract
Background
Recent studies have investigated the association of transitions in metabolic health and obesity status over time with the risk of cardiovascular disease, focusing on the subgroup demonstrating metabolically healthy obesity. However, these studies have produced inconsistent results. This study evaluates the relation in a general Chinese population.
Methods
We conducted a prospective cohort study in a general population in Northeast China, with examinations of cardiovascular health from 2012–2015 and follow-up for incident cardiovascular disease until 2018. Cox proportional hazards and logistic regression models were used to investigate the association of baseline metabolic health and obesity status and transitions in those statuses with cardiovascular disease risk.
Results
A total of 7472 participants aged ≥35 years who were free of cardiovascular disease at baseline were included in this analysis. Over a median follow-up of 4.66 years, a total of 344 cardiovascular disease events occurred. Among the 3380 participants who were obese at baseline, 37.1% were metabolically healthy. Metabolically healthy obesity was associated with a 48% increased risk of cardiovascular disease (hazard ratio: 1.48; 95% confidence interval: 1.07–2.06) compared with the metabolically healthy non-obese group at baseline. Transition from metabolically healthy obesity to metabolically unhealthy obesity was associated with elevated cardiovascular disease risk with an odds ratio of 1.82 (95% confidence interval: 1.06–3.14) compared with metabolically healthy non-obesity throughout after adjustment. Even maintaining metabolically healthy obesity over time was associated with a higher risk of cardiovascular disease (odds ratio: 1.72; 95% confidence interval: 1.00–2.97).
Conclusions
Weight control and management of existing metabolic disorders should be prioritized in all obese population.
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Affiliation(s)
- Xiaofan Guo
- Department of Cardiology, The First Hospital of China Medical University, China
| | - Zhao Li
- Department of Cardiology, The First Hospital of China Medical University, China
| | - Ying Zhou
- Department of Cardiology, The First Hospital of China Medical University, China
| | - Shasha Yu
- Department of Cardiology, The First Hospital of China Medical University, China
| | - Hongmei Yang
- Department of Cardiology, The First Hospital of China Medical University, China
| | - Guozhe Sun
- Department of Cardiology, The First Hospital of China Medical University, China
| | - Liqiang Zheng
- Department of Clinical Epidemiology, Library, Shengjing Hospital of China Medical University, China
| | - Junaid Afzal
- Division of Cardiology, University of California, USA
| | - Yamin Liu
- Division of Cardiology, University of California, USA
| | - Yingxian Sun
- Department of Cardiology, The First Hospital of China Medical University, China
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21
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Abstract
PURPOSE OF REVIEW To present a comprehensive overview regarding criteria, epidemiology, and controversies that have arisen in the literature about the existence and the natural course of the metabolic healthy phenotype. RECENT FINDINGS The concept of metabolically healthy obesity (MHO) implies that a subgroup of obese individuals may be free of the cardio-metabolic risk factors that commonly accompany obese subjects with adipose tissue dysfunction and insulin resistance, known as having metabolic syndrome or the metabolically unhealthy obesity (MUO) phenotype. Individuals with MHO appear to have a better adipose tissue function, and are more insulin sensitive, emphasizing the central role of adipose tissue function in metabolic health. The reported prevalence of MHO varies widely, and this is likely due the lack of universally accepted criteria for the definition of metabolic health and obesity. Also, the natural course and the prognostic value of MHO is hotly debated but it appears that it likely evolves towards MUO, carrying an increased risk for cardiovascular disease and mortality over time. Understanding the pathophysiology and the determinants of metabolic health in obesity will allow a better definition of the MHO phenotype. Furthermore, stratification of obese subjects, based on metabolic health status, will be useful to identify high-risk individuals or subgroups and to optimize prevention and treatment strategies to compact cardio-metabolic diseases.
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Affiliation(s)
- Agathocles Tsatsoulis
- Department of Endocrinology, School of Health Sciences, University of Ioannina, 451 10, Ioannina, Greece.
| | - Stavroula A Paschou
- Division of Endocrinology and Diabetes, "Aghia Sophia" Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
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22
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Gállego-Suárez C, Bulan A, Hirschfeld E, Wachowiak P, Abrishami S, Griffin C, Sturza J, Tzau A, Hayes T, Woolford SJ, Lumeng CN, Lee JM, Singer K. Enhanced Myeloid Leukocytes in Obese Children and Adolescents at Risk for Metabolic Impairment. Front Endocrinol (Lausanne) 2020; 11:327. [PMID: 32528415 PMCID: PMC7266967 DOI: 10.3389/fendo.2020.00327] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 04/27/2020] [Indexed: 12/26/2022] Open
Abstract
Objective: We aimed to examine if myeloid leukocyte profiles are associated with metabolic impairment in children and adolescents with obesity, and if sex, age, or race influence this relationship. Methods: 282 children ages 8-17 were evaluated. Predictor measures were absolute neutrophil counts (ANC), absolute monocyte count, monocyte subtypes and C reactive protein (CRP). Outcome variables were waist circumference, fasting glucose and insulin, HOMA-IR, HbA1c (%) and lipid profiles. Pearson correlation coefficients were used to determine associations between predictor and outcome variables. Wilcoxon two-sample tests were used to evaluate differences by sex. Results: CRP (p < 0.0001), ANC (p < 0.0018), and classical monocytes (p = 0.05) were significantly higher in children with obesity. CRP, ANC and classical monocytes showed positive correlations with waist circumference, insulin, HOMA-IR and triglycerides. CRP was positively associated with ANC overall (p = 0.05). ANC demonstrated positive correlation with monocytes (p < 0.001). The associations between predictor and outcome variables were influenced by sex, race, and age. Conclusions: CRP and myeloid leukocyte populations, specifically classical monocytes and neutrophils associate with both body composition and metabolic parameters in children with obesity suggesting that these cells may play a critical role in metabolic impairment. Race, gender and age interactions between monocytes and metabolic parameters were significant.
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Affiliation(s)
- Cecilia Gállego-Suárez
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
| | - Ayse Bulan
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
| | - Emily Hirschfeld
- Department of Pediatrics, Child Health Evaluation and Research Center (CHEAR), University of Michigan, Ann Arbor, MI, United States
| | - Phillip Wachowiak
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
| | - Simin Abrishami
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
| | - Cameron Griffin
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
| | - Julie Sturza
- Woodson Biostatistics Consultation Program, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
| | - Abigail Tzau
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
| | - Taryn Hayes
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
| | - Susan J. Woolford
- Department of Pediatrics, Child Health Evaluation and Research Center (CHEAR), University of Michigan, Ann Arbor, MI, United States
| | - Carey N. Lumeng
- Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI, United States
- Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Joyce M. Lee
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
- Department of Pediatrics, Child Health Evaluation and Research Center (CHEAR), University of Michigan, Ann Arbor, MI, United States
| | - Kanakadurga Singer
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, United States
- Graduate Program in Immunology, University of Michigan Medical School, Ann Arbor, MI, United States
- Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI, United States
- *Correspondence: Kanakadurga Singer
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