Correlation of adiponectin receptor expression with cytokines and insulin sensitivity in growth hormone (GH)-treated children with Prader-Willi syndrome and in non-GH-treated obese children.
BACKGROUND
Prader-Willi syndrome (PWS), a genetic disorder characterized by obesity in early childhood, is reported to have elevated levels of adiponectin. The effects of adiponectin are mediated by adiponectin receptors (ADIPORs) that include ADIPOR1 and ADIPOR2. There is evidence that several cytokines, including adiponectin, TNF-alpha, and IL-6, are involved in insulin sensitivity.


OBJECTIVE
We measured the relative expression of adiponectin, ADIPORs, several proinflammatory cytokines including TNF-alpha, and IL-6 expression in peripheral blood mononuclear cells (PBMCs) of children with PWS and obese comparators using real-time PCR. Their correlation with homeostasis model assessment insulin resistance index (HOMA-IR) was analyzed.


METHODS
Thirty children with PWS (median age 7.1 yr, 18 males, 12 females) that were being treated with GH and 32 obese children not receiving GH treatment (median age 9.1 yr, 15 males, 17 females) for comparison were enrolled.


RESULTS
The PWS children had increased expression of ADIPOR2 (P = 0.02) and decreased expression of IL-6 (P = 0.03) compared with the comparison group. Moreover, there was a significant positive correlation between the ADIPORs and TNF-alpha (ADIPOR1 vs. TNF-alpha: r = 0.66, P < 0.001 in PWS, r = 0.80, P < 0.001 in comparison group; ADIPOR2 vs. TNF-alpha: r = 0.69, P < 0.001 in comparison group). The ADIPORs in the comparison group showed significant negative correlation with HOMA-IR (ADIPOR1 vs. HOMA-IR; rho = -0.41, P = 0.02, ADIPOR2 vs. HOMA-IR; rho = -0.46, P < 0.01).


CONCLUSIONS
The results of this study showed that inflammatory cytokine expression was closely associated with the expression of the ADIPORs in the PBMCs of both the children with PWS and the comparison group. Moreover, ADIPOR2 expression was highly expressed in the PBMCs of the children with PWS. A further study on the mechanism of increased expression of ADIPOR2 and its correlation with the expression of TNF-alpha in the PBMCs using the non-GH-treated PWS and obese control will be warranted because this study compared GH-treated PWS with an obese comparator group.
Sohn
Young Bae
YB
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Il-Won Dong, Gang-Nam Gu, Seoul 135-710, Korea.
Kwak
Min Jung
MJ
Kim
Su Jin
SJ
Park
Sung Won
SW
Kim
Chi Hwa
CH
Kim
Mi Young
MY
Kwon
Eun Kyung
EK
Paik
Kyung Hoon
KH
Jin
Dong-Kyu
DK
D000293:Adolescent; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D018579:Patient Selection; D011218:Prader-Willi Syndrome / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D007328:Insulin; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D019382:Human Growth Hormone