Adipose Tissue Remodeling in Children: The Link between Collagen Deposition and Age-Related Adipocyte Growth

被引:37
作者
Tam, Charmaine S. [1 ,2 ,3 ,4 ]
Tordjman, Joan [3 ,4 ]
Divoux, Adeline [3 ,4 ]
Baur, Louise A. [2 ]
Clement, Karine [3 ,4 ,5 ]
机构
[1] Childrens Hosp Westmead, Inst Endocrinol & Diabet, Westmead, NSW 2145, Australia
[2] Univ Sydney, Childrens Hosp Westmead, Sch Clin, Discipline Paediat & Child Hlth, Westmead, NSW 2145, Australia
[3] INSERM, U872, Inst Cardiometab & Nutr, F-75006 Paris, France
[4] Univ Paris 06, Ctr Rech Cordeliers, Unite Mixte Rech Sante 872, F-75006 Paris, France
[5] Hop La Pitie Salpetriere, Assistance Publ Hop Paris, Div Nutr, F-75013 Paris, France
基金
英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词
EXTRACELLULAR-MATRIX; INSULIN-RESISTANCE; MACROPHAGE INFILTRATION; OBESE CHILDREN; WEIGHT; DIFFERENTIATION; ADOLESCENTS; CHILDHOOD; FIBROSIS; HUMANS;
D O I
10.1210/jc.2011-2806
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: Extracellular matrix (ECM) remodeling is essential for adipose tissue growth and expansion in high fat-fed mice, and there is evidence of fibrosis in adipose tissue in human obesity. Objective: The aim of the study was to explore the role of ECM remodeling in adipose tissue in healthy, growing children. Research Design, Setting, and Participants: Abdominal sc adipose biopsies were obtained from 65 otherwise healthy children [57 boys; age, 5.3 +/- 3.8 yr (mean +/- SD)] having elective surgery (cross-sectional study). Twenty percent of the participants were classified as overweight/obese based on body mass index (BMI) z score. Main Outcome Measures: We examined collagen (total and pericellular), HAM56+ macrophages, CD206+ M2 phenotype macrophages, and CD3+ T cells measured by immunohistochemistry and ECM gene expression markers. Results: Overweight children had significantly less total collagen compared to normal weight children (median, 3.4 vs. 9.1%; P = 0.001). However, collagen areas were not positive for COL6 and showed little evidence of collagen surrounding adipocytes. Fat cell size was negatively correlated with the percentage of total (r = -0.398; P = 0.003) and pericellular collagen (r = -0.462; P < 0.001) but positively correlated with HAM56+ macrophages (r = 0.541; P < 0.001). The percentage of total collagen was inversely associated with BMI z score (r = -0.345; P = 0.01) and age (r = -0.348; P = 0.005), with older (> 11 yr old) children in the top BMI z tertile having less collagen (3.8%) than younger (2-5 yr old) children in the bottom BMI z tertile (12.6%). Adipose tissue in overweight children showed little evidence of crown-like structures or T cells. Conclusion: In healthy, growing children, increased collagen in adipose tissue is associated with decreased fat cell size and BMI z score and increased M2+ phenotype macrophages, suggesting dynamic interaction between ECM remodeling and immune cells even at an early age. (J Clin Endocrinol Metab 97: 1320-1327, 2012)
引用
收藏
页码:1320 / 1327
页数:8
相关论文
共 27 条
[1]   Adipose macrophage infiltration is associated with insulin resistance and vascular endothelial dysfunction in obese subjects [J].
Apovian, Caroline M. ;
Bigornia, Sherman ;
Mott, Melanie ;
Meyers, Melissa R. ;
Ulloor, Jagadish ;
Gagua, Manana ;
McDonnell, Marie ;
Hess, Donald ;
Joseph, Lija ;
Gokce, Noyan .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2008, 28 (09) :1654-1659
[2]   High molecular weight, rather than total, adiponectin levels better reflect metabolic abnormalities associated with childhood obesity [J].
Araki, Shunsuke ;
Dobashi, Kazushige ;
Kubo, Kazuyasu ;
Asayama, Kohtaro ;
Shirahata, Akira .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (12) :5113-5116
[3]   Human Adipose Tissue Macrophages: M1 and M2 Cell Surface Markers in Subcutaneous and Omental Depots and after Weight Loss [J].
Aron-Wisnewsky, Judith ;
Tordjman, Joan ;
Poitou, Christine ;
Darakhshan, Froogh ;
Hugol, Danielle ;
Basdevant, Arnaud ;
Aissat, Abdelhalim ;
Guerre-Millo, Michele ;
Clement, Karine .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2009, 94 (11) :4619-4623
[4]   Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery induced weight loss [J].
Cancello, R ;
Henegar, C ;
Viguerie, N ;
Taleb, S ;
Poitou, C ;
Rouault, C ;
Coupaye, M ;
Pelloux, V ;
Hugol, D ;
Bouillot, JL ;
Bouloumié, A ;
Barbatelli, G ;
Cinti, S ;
Svensson, PA ;
Barsh, GS ;
Zucker, JD ;
Basdevant, A ;
Langin, D ;
Clément, K .
DIABETES, 2005, 54 (08) :2277-2286
[5]   Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans [J].
Cinti, S ;
Mitchell, G ;
Barbatelli, G ;
Murano, I ;
Ceresi, E ;
Faloia, E ;
Wang, SP ;
Fortier, M ;
Greenberg, AS ;
Obin, MS .
JOURNAL OF LIPID RESEARCH, 2005, 46 (11) :2347-2355
[6]  
CINTI S, 1984, J SUBMICR CYTOL PATH, V16, P243
[7]   Establishing a standard definition for child overweight and obesity worldwide: international survey [J].
Cole, TJ ;
Bellizzi, MC ;
Flegal, KM ;
Dietz, WH .
BMJ-BRITISH MEDICAL JOURNAL, 2000, 320 (7244) :1240-1243
[8]   Indexes of insulin resistance and secretion in obese children and adolescents - A validation study [J].
Conwell, LS ;
Trost, SG ;
Brown, WJ ;
Batch, JA .
DIABETES CARE, 2004, 27 (02) :314-319
[9]   Defining macrophage phenotype and function in adipose tissue [J].
Dalmas, Elise ;
Clement, Karine ;
Guerre-Millo, Michele .
TRENDS IN IMMUNOLOGY, 2011, 32 (07) :307-314
[10]   CRITICAL PERIODS IN CHILDHOOD FOR THE DEVELOPMENT OF OBESITY [J].
DIETZ, WH .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1994, 59 (05) :955-959