T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity.
BACKGROUND
Obesity is associated with chronic inflammation, which includes increased macrophage accumulation in adipose tissue (AT) and upregulation of chemokines and cytokines. T cells also play important roles in chronic inflammatory diseases such as atherosclerosis but have not been well studied in obesity.


RESULTS
Flow cytometric analysis showed higher numbers of T cells and macrophages in AT of diet-induced obese insulin-resistant male mice than in lean mice and obese females (P<0.05). RNase protection assay, ELISA, and flow cytometry indicated gender-dependent upregulation of mRNA and protein levels of regulated on activation, normal T cell expressed and secreted (RANTES) and its receptor CCR5 in AT of obese mice. Adipocytes, stromal/vascular cells from mouse AT, and human and murine adipocytes expressed RANTES. RANTES mRNA levels were negatively correlated with adiponectin in mouse AT. Adiponectin-deficient mice fed high-fat diet showed higher RANTES mRNA levels in AT than wild-type mice. Activated T cells coincubated with preadipocytes in vitro significantly suppressed preadipocyte-to-adipocyte differentiation. Obese humans with metabolic syndrome had higher mRNA levels of RANTES and CCR5 in subcutaneous AT than lean humans. RANTES and CCR5 mRNA levels were significantly higher in visceral than subcutaneous AT of morbidly obese humans. RANTES mRNA levels were positively correlated with CD3 and CD11b in human visceral AT.


CONCLUSIONS
Obesity is associated with increased accumulation of T cells and macrophages in AT, which may play important roles in obesity-related disease by influencing preadipocyte/adipocyte functions. RANTES is an adipokine that is upregulated in AT by obesity in both mice and humans.
Wu
Huaizhu
H
Section of Atherosclerosis and Vascular Medicine, Baylor College of Medicine, 6565 Fannin, Houston, TX 77030, USA.
Ghosh
Sudip
S
Perrard
Xiaoyuan Dai
XD
Feng
Lili
L
Garcia
Gabriela E
GE
Perrard
Jerry L
JL
Sweeney
John F
JF
Peterson
Leif E
LE
Chan
Lawrence
L
Smith
C Wayne
CW
Ballantyne
Christie M
CM
D017667:Adipocytes / Q000737:chemistry; D052242:Adiponectin / Q000235:genetics / Q000502:physiology*; D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D039481:CD11b Antigen / Q000235:genetics; D017252:CD3 Complex / Q000235:genetics; D002454:Cell Differentiation; D018946:Chemokine CCL5 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002630:Chemotactic Factors / Q000032:analysis; D005260:Female; D006801:Humans; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D019713:Receptors, CCR5 / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D015854:Up-Regulation
D052242:Adiponectin; D039481:CD11b Antigen; D017252:CD3 Complex; D018946:Chemokine CCL5; D002630:Chemotactic Factors; D012333:RNA, Messenger; D019713:Receptors, CCR5