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Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10434-9. Epub 2004 Jul 1.

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity.

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  • 1Center for Pharmacogenomics and Clinical Pharmacology, Neuropsychiatric Institute, Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1761, USA.


Ghrelin plays a key role in the regulation of growth hormone secretion and energy homeostasis. Adiponectin is exclusively secreted by adipose tissue and is abundantly present in the circulation, with important effects on metabolism. We studied five lean and five obese young men [ages: 24.2 +/- 1.0 (lean) and 21.8 +/- 1.6 (obese) years (difference not significant); body mass indexes: 35.0 +/- 1.3 and 23.0 +/- 0.3 kg/m2 (P = 0.01)], sampled blood every 7 min over 24 h, and measured ghrelin, adiponectin, and leptin in 2,070 samples for a total of 6,210 data points. Circulating 24-h ghrelin showed significant ultradian fluctuations and an orderly pattern of release in lean and obese subjects with similar pulsatility characteristics. Plasma adiponectin concentrations were significantly lower in the obese group, with lower pulse height. In contrast to leptin, which is secreted in an orderly manner, the 24-h patterns of adiponectin were not significantly different from random in both the lean and obese groups. We show here that adipocytes can simultaneously secrete certain hormones, such as leptin, in patterns that are orderly, whereas other hormones, such as adiponectin, are secreted in patterns that appear to be random. The cross-approximate entropy statistic revealed pattern synchrony among ghrelin-leptin, ghrelin-adiponectin, and leptin-adiponectin hormone time series in the lean and obese subjects. Plasma ghrelin concentrations showed a nocturnal rise that exceeded the meal-associated increases in lean subjects, and this newly identified nocturnal rise was blunted in the obese. We suggest that the blunting of the nocturnal rise of ghrelin is a biological feature of human obesity.

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