Evidence of early alterations in adipose tissue biology and function and its association with obesity-related inflammation and insulin resistance in children.
Accumulation of fat mass in obesity may result from hypertrophy and/or hyperplasia and is frequently associated with adipose tissue (AT) dysfunction in adults. Here we assessed early alterations in AT biology and function by comprehensive experimental and clinical characterization of 171 AT samples from lean and obese children aged 0 to 18 years. We show an increase in adipocyte size and number in obese compared with lean children beginning in early childhood. These alterations in AT composition in obese children were accompanied by decreased basal lipolytic activity and significantly enhanced stromal vascular cell proliferation in vitro, potentially underlying the hypertrophy and hyperplasia seen in obese children, respectively. Furthermore, macrophage infiltration, including the formation of crown-like structures, was increased in AT of obese children from 6 years on and was associated with higher hs-CRP serum levels. Clinically, adipocyte hypertrophy was not only associated with leptin serum levels but was highly and independently correlated with HOMA-IR as a marker of insulin resistance in children. In summary, we show that adipocyte hypertrophy is linked to increased inflammation in AT in obese children, thereby providing evidence that obesity-associated AT dysfunction develops in early childhood and is related to insulin resistance.
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany Integrated Research and Treatment Center IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Kathrin
K
Landgraf
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany Integrated Research and Treatment Center IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Denise
D
Rockstroh
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
Isabel V
IV
Wagner
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany Integrated Research and Treatment Center IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Sebastian
S
Weise
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
Roy
R
Tauscher
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
Julian T
JT
Schwartze
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany Integrated Research and Treatment Center IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany.
Dennis
D
Löffler
Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany.
Ulf
U
Bühligen
Department of Orthopedic Surgery, University of Leipzig, Leipzig, Germany.
Magdalena
M
Wojan
Integrated Research and Treatment Center IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany Department of Pediatric and Adolescent Surgery, Medical University of Graz, Graz, Austria.
Holger
H
Till
Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Leipzig, Germany.
Jürgen
J
Kratzsch
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany.
Wieland
W
Kiess
Integrated Research and Treatment Center IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany Department of Medicine, Division of Endocrinology, University of Leipzig, Leipzig, Germany.
Matthias
M
Blüher
Center for Pediatric Research Leipzig, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany Integrated Research and Treatment Center IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany antje.koerner@medizin.uni-leipzig.de.
Antje
A
Körner
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism / Q000503:physiopathology*; D000293:Adolescent; D001786:Blood Glucose; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin