Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity - PubMed (original) (raw)

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

Bulent O Yildiz et al. Proc Natl Acad Sci U S A. 2004.

Abstract

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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Figures

Fig. 1.

Fig. 1.

Twenty-four-hour profiles of rapidly sampled plasma ghrelin (a) and adiponectin (b) in lean (blue) and obese (red) male subjects. Arrows indicate standardized meals (breakfast, lunch, dinner, and evening snack), and the sleep period is demarcated by a black strip. Blood samples were collected in a general clinical research center after two nights of acclimatization in the research room. Lights were on during 0700–2300 hours and off during 2300–0700 hours, during which time subjects slept.

Fig. 2.

Fig. 2.

Twenty-four-hour profiles of rapidly sampled plasma leptin in lean (blue) and obese (red) male subjects. Arrows indicate standardized meals (breakfast, lunch, dinner, and evening snack), and the sleep period is demarcated by a black strip. Blood samples were collected in a general clinical research center after two nights of acclimatization in the research room. Lights were on during 0700–2300 hours and off during 2300–0700 hours, during which time subjects slept.

Fig. 3.

Fig. 3.

Estimated 24-h profiles of plasma ghrelin, adiponectin, and leptin in lean (a_–_c) and obese (d_–_f) subjects. For each group, mean hormone levels are plotted as circles. The semiparametric linear mixed-effects model, across-subject prediction is drawn as a solid line. Dashed lines trace out the prediction's approximate 95% confidence interval. Arrows indicate standardized meals (breakfast, lunch, dinner, and evening snack), and the sleep period is demarcated by a black strip.

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