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

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 kg͞m 2 (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 leptinadiponectin 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.

Sex-specific determinants of serum adiponectin in older adults: the role of endogenous sex hormones

“…Serum adiponectin values were measured on a single sample, which may have limited associations; however, adiponectin levels show minimal diurnal variation, are stable during the morning hours when these samples were collected and single measurements have been shown to accurately reflect levels over a 1-year period. [50][51][52][53] It is not known whether long-term storage effects adiponectin levels; in this cohort, adiponectin concentrations were not significantly related to storage time, and levels were similar to published values for individuals of comparable age and adiposity. 3,5 Endogenous sex hormones and adiponectin GA Laughlin et al Adiponectin circulates in complex structures, predominantly a low-and a high-molecular weight (HMW) form.…”

Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion

“…In pulse-chase experiments, only a fraction, up to 50%, of the labeled leptin that disappeared from cells could be recovered in the medium, suggesting that some of the newly synthesized leptin is degraded within adipose tissue (38). Insulin prevented this intracellular leptin degradation by moving it out of the cells, increasing the half-life of newly (44,47,86) to illustrate that obesity is associated with higher fasting leptin levels and higher meal-induced leptin excursions. We hypothesize that this occurs, at least in part, as a result of increased secretion of preformed leptin from the LFC of the obese.…”

Biological aging alters circadian mechanisms in murine adipose tissue depots

“…Eating during periods of darkness (Holmback et al 2002(Holmback et al , 2003Spiegel et al 2004) and antipsychotic drugs influencing circadian rhythms such as lithium chloride and valproic acid (Baptista et al 1995;Elmslie et al 2001;Atmaca et al 2002;Chengappa et al 2002;Fagiolini et al 2002Fagiolini et al , 2003Iwahana et al 2004) have been associated with an increased incidence of obesity. The serum levels of multiple adipose-derived proteins, including adiponectin, interleukin-6, leptin, lipoprotein lipase, PAI-1, and tumor necrosis factor-α, display a diurnal profile characterized by a distinct amplitude, zenith (peak), and nadir (trough) (Kotlar and Borensztajn 1977;Goubern and Portet 1981;Saad et al 1998;Ahmad et al 2001;Arasaradnam et al 2002;Mastronardi et al 2002;Gavrila et al 2003;Calvani et al 2004;Ruge et al 2004;Yildiz et al 2004). Moreover, transcription factors regulating adipocyte gene markers (PPARα, Rev-Erbα, SREBP) display a circadian expression profile (Lemberger et al 1996;Torra et al 2000;Patel et al 2001).…”