Fasting Plasma Ghrelin Levels Are Negatively Correlated With Insulin Resistance and PAI-1, but Not With Leptin, in Obese Children and Adolescents

  1. Ayako Ikezaki1,
  2. Hiroshi Hosoda23,
  3. Keiko Ito1,
  4. Saika Iwama1,
  5. Naoko Miura1,
  6. Hisafumi Matsuoka1,
  7. Chisato Kondo4,
  8. Masayasu Kojima5,
  9. Kenji Kangawa23 and
  10. Shigetaka Sugihara1
  1. 1Department of Pediatrics, Tokyo Women’s Medical University Daini Hospital, Tokyo, Japan
  2. 2Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka, Japan
  3. 3Translational Research Center, Kyoto University Hospital, Kyoto, Japan
  4. 4Department of Pediatric Cardiology, Heart Institute of Japan, Tokyo Women’s Medical University, Tokyo, Japan
  5. 5Institute of Life Science, Kurume University, Kurume, Japan

    Abstract

    Ghrelin is a novel growth hormone−releasing peptide isolated from human and rat stomach that induces weight gain by increasing food intake and reducing fat utilization. Although recent data indicate that ghrelin is downregulated in human adult obesity, the characteristics of human obesity are heterogeneous, especially in children and adolescents, and depend on the distribution of subcutaneous and visceral fat tissue. We measured fasting plasma ghrelin concentrations by radioimmunoassay in 49 obese Japanese children and adolescents (38 boys and 11 girls; mean age 10.2 ± 2.8 years; BMI 28.0 ± 4.5 kg/m2, percent overweight 56.0 ± 20.7%), and analyzed associations of their ghrelin concentrations with their body composition, insulin resistance, and adipocytokine concentrations. Fasting plasma ghrelin levels were negatively correlated with BMI and waist circumference, but not with percent overweight or percent body fat, whereas fasting leptin levels were positively correlated with all of the following parameters: BMI, waist circumference, percent overweight, and percent body fat. Plasma ghrelin levels were negatively correlated with fasting immunoreactive insulin, homeostasis model assessment insulin resistance index, and quantitative insulin sensitivity check index values. There was no correlation between plasma ghrelin and leptin, but ghrelin was negatively correlated with the PAI-1 concentrations. The results suggest that the downregulation of ghrelin secretion may be a consequence of higher insulin resistance associated with visceral fat accumulation and elevated PAI-1 concentrations, and not a consequence of total body fat accumulation associated with elevated leptin concentrations.

    Footnotes

    • Address correspondence and reprint requests to Dr. Shigetaka Sugihara, Department of Pediatrics, Tokyo Women’s Medical University Daini Hospital, 2-1-10, Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan. E-mail: sugihapd{at}dnh.twmu.ac.jp.

      Received for publication 27 March 2002 and accepted in revised form 4 September 2002.

      FBG, fasting blood glucose; GH, growth hormone; HOMA-R, homeostasis model assessment insulin resistance index; IRI, immunoreactive insulin; PAI-1, plasminogen activator inhibitor-1; QUICKI, quantitative insulin sensitivity check index; RIA, radioimmunoassay.

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