Circulating Adropin Concentrations in Pediatric Obstructive Sleep Apnea: Potential Relevance to Endothelial Function

Abstract

Objective To test the hypothesis that levels of adropin, a recently discovered peptide that displays important metabolic and cardiovascular functions, are lower in obstructive sleep apnea (OSA), especially when associated with endothelial dysfunction. Study design Age-, sex- and ethnicity-matched children (mean age: 7.2±1.4 years) were included into one of three groups based on the presence of OSA in an overnight sleep study, and on the time to post-occlusive maximal reperfusion (Tmax>45 sec) with a modified hyperemic test. Plasma adropin levels were assayed using a commercial ELISA kit. Results Among controls, mean morning adropin levels were 7.4 ng/ml (95% confidence intervals: 5.2–16.3 ng/ml) OSA children with abnormal endothelial function (OSA+/EF+) had significantly lower adropin levels (2.7±1.1 ng/ml, n=35) compared with matched controls (7.6±1.4 ng/ml; n=35; p<0.001), and to children with OSA and normal endothelial function (OSA+/EF−: 5.8±1.5 ng/ml, n=47; p<0.001). Plasma adropin <4.2 ng/ml reliably predicted endothelial functional status, but individual adropin levels were not significantly correlated with age, BMI-z score, obstructive apnea-hypopnea index (AHI) or nadir SpO2. Adropin levels were assessed after adenotonsillectomy in a subset of children with OSA (n=22), and showed increases in OSA+/EF+ (2.5±1.4 ng/ml to 6.4±1.9 ng/ml, n=14; p<0.01) but remained unchanged in OSA+EF− (5.7±1.3 ng/ml to 6.4±1.1 ng/ml, n=8; p>0.05). Conclusion Plasma adropin levels are reduced in pediatric OSA when endothelial dysfunction is present, and return to within normal values after adenotonsillectomy. Assessment of adropin circulating levels may provide a reliable indicator of vascular injury in the context of OSA on children.

Adropin Is a Brain Membrane-bound Protein Regulating Physical Activity via the NB-3/Notch Signaling Pathway in Mice

“…Because adropin had been proposed as a hepatocyte-secreted protein (1), it was expected that adropin could be found in the liver and blood samples. The controversial findings regarding circulating adropin (6,8,9,13) led us to reinvestigate the biochemical properties of adropin.…”

“…Correlations between circulating adropin levels and different pathophysiological states in mice and humans have been reported (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In brief, the circulating concentration of adropin was reduced markedly in several metabolic diseases, including obesity-associated insulin resistance (1,5,11); obesity-related, nonalcoholic fatty liver disease (11); gestational diabetes mellitus (7); and endothelial dysfunction (6,8,14). However, conversely, other studies found that plasma adropin levels in humans were not correlated inversely with obesity on the basis of body mass index (6,8,13) or with endothelial dysfunction (9).…”

“…In brief, the circulating concentration of adropin was reduced markedly in several metabolic diseases, including obesity-associated insulin resistance (1,5,11); obesity-related, nonalcoholic fatty liver disease (11); gestational diabetes mellitus (7); and endothelial dysfunction (6,8,14). However, conversely, other studies found that plasma adropin levels in humans were not correlated inversely with obesity on the basis of body mass index (6,8,13) or with endothelial dysfunction (9). In addition, unlike findings in mice, plasma adropin levels in humans do not change in response to fasting and refeeding (5).…”

Adropin induction of lipoprotein lipase expression in tilapia hepatocytes

“…Even though the linkage between circulating adropin levels and other various pathophysiological conditions in mammals have been reported, the exact link with adropin remains elusive. Some studies showed that plasma adropin levels were linked with several metabolic diseases, including insulin resistance ) and nonalcoholic fatty liver disease (Sayin et al 2014) and endothelial dysfunction (Gozal et al 2013), whereas other studies found that plasma adropin levels were not correlated with endothelial dysfunction in humans with heart failure (Lian et al 2011) or with BMI in patients with type 2 diabetes mellitus (Topuz et al 2013). Besides, adropin may be involved in the metabolic adaptation to fasting, although these data are still controversial.…”

Pediatric OSA Syndrome Morbidity Biomarkers

“…20 Over the last decade, a constellation of morbidity-related biomarkers has been proposed for pediatric OSAS, and a scoping review was previously published and investigated potential associations and predictive abilities of such published candidate biomarkers in OSAS-induced morbidities in both adults and children. 21 In this article, we focus on the more promising of such biomarkers, and particularly on those potentially contributing to detection and monitoring of cardiometabolic morbidity (see Table 1 [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] residual OSAS following T&A. 23 On the basis of the interindividual variability of the responses to T&A we previously found in a large panel of inflammatory markers among a large group of obese children with OSAS, 24 it is likely that use of CRP alone, rather than as a component of a multiarray panel, may not provide sufficiently accurate prediction of CVD risk or its resolution with treatment.…”