Systemic inflammation in childhood obesity: circulating inflammatory mediators and activated CD14++ monocytes

被引：99

作者：

Schipper, H. S. ^{[1
,2
,3
]}

Nuboer, R. ^{[4
]}

Prop, S. ^{[1
]}

van den Ham, H. J. ^{[5
]}

de Boer, F. K. ^{[6
]}

Kesmir, C. ^{[6
]}

Mombers, I. M. H. ^{[2
,3
]}

van Bekkum, K. A. ^{[2
,3
]}

Woudstra, J. ^{[1
]}

Kieft, J. H. ^{[2
,3
]}

Hoefer, I. E. ^{[7
]}

de Jager, W. ^{[2
,3
]}

Prakken, B. ^{[2
,3
]}

van Summeren, M. ^{[8
]}

Kalkhoven, E. ^{[1
]}

机构：

[1] Univ Med Ctr Utrecht, Dept Metab Dis, NL-3584 CG Utrecht, Netherlands

[2] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Pediat Immunol, NL-3584 CG Utrecht, Netherlands

[3] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Ctr Mol & Cellular Intervent, NL-3584 CG Utrecht, Netherlands

[4] Meander Med Ctr, Dept Pediat, Amersfoort, Netherlands

[5] Erasmus MC, Dept Virol, Rotterdam, Netherlands

[6] Univ Utrecht, Dept Theoret Biol & Bioinformat, Utrecht, Netherlands

[7] Univ Med Ctr Utrecht, Lab Expt Cardiol, NL-3584 CG Utrecht, Netherlands

[8] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Pediat, NL-3584 CG Utrecht, Netherlands

来源：

DIABETOLOGIA | 2012年 / 55卷 / 10期

关键词：

Adipokines; Childhood obesity; Inflammation; Insulin resistance; Monocytes; BODY-MASS INDEX; INDUCED INSULIN-RESISTANCE; OVERWEIGHT CHILDREN; METABOLIC DISEASE; ATHEROSCLEROSIS; CD11B; RISK; EXPRESSION; LEUKOCYTES; MIGRATION;

D O I：

10.1007/s00125-012-2641-y

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In adults, circulating inflammatory mediators and activated CD14(++) monocytes link obesity to its metabolic and cardiovascular complications. However, it is largely unknown whether these inflammatory changes already occur in childhood obesity. To survey inflammatory changes during the early stages of obesity, we performed a comprehensive analysis of circulating inflammatory mediators, monocyte populations and their function in childhood obesity. In lean and obese children aged 6 to 16 years (n = 96), 35 circulating inflammatory mediators including adipokines were measured. Hierarchical cluster analysis of the inflammatory mediator profiles was performed to investigate associations between inflammatory mediator clusters and clinical variables. Whole-blood monocyte phenotyping and functional testing with the toll-like receptor 4 ligand, lipopolysaccharide, were also executed. First, next to leptin, the circulating mediators chemerin, tissue inhibitor of metalloproteinase 1, EGF and TNF receptor 2 were identified as novel inflammatory mediators that are increased in childhood obesity. Second, cluster analysis of the circulating mediators distinguished two obesity clusters, two leanness clusters and one mixed cluster. All clusters showed distinct inflammatory mediator profiles, together with differences in insulin sensitivity and other clinical variables. Third, childhood obesity was associated with increased CD14(++) monocyte numbers and an activated phenotype of the CD14(++) monocyte subsets. Inflammatory mediator clusters were associated with insulin resistance in obese and lean children. The activation of CD14(++) monocyte subsets, which is associated with increased development of atherosclerosis in obese adults, was also readily detected in obese children. Our results indicate that inflammatory mechanisms linking obesity to its metabolic and cardiovascular complications are already activated in childhood obesity.

引用

页码：2800 / 2810

页数：11