The Association of the Hypothalamic-Pituitary-Adrenal Axis with Appetite Regulation in Children with Fetal Alcohol Spectrum Disorders (FASDs)

Abstract

Prenatal alcohol exposure causes growth impairment and a wide range of developmental, physical, and cognitive disorders in children, collectively referred to as fetal alcohol spectrum disorders (FASDs). In the course of FASDs, abnormalities can also affect eating behavior and nutritional status, but these problems have received little attention. Therefore, the aim of our study was to determine the levels of hormones involved in the action of the hypothalamic–pituitary–adrenal axis: proopiomelanocortin (POMC), cortisol, and adrenocorticotropic hormone (ACTH), in the serum of patients with FASDs. To our knowledge, none of these hormones studied have yet been evaluated in FASDs to date. We investigated 62 FASD patients and 23 healthy controls by applying an enzyme-linked immunosorbent method (ELISA). Fasting POMC levels were significantly lower in patients with FASDs (10.97 vs. 18,57 ng/mL, p = 0.039) compared to controls. However, there were no differences in cortisol concentrations. Additionally, the sex and subgroup status (fetal alcohol syndrome (FAS), neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE), and FASD risk) did not affect hormone levels. POMC was positively correlated with some clinical parameters such as age, BMI percentile, carbohydrate biomarkers, and ACTH. A positive correlation was observed between ACTH and cortisol levels, as well as ACTH and cholesterol levels. Data analysis showed no HPA axis abnormalities in the form of elevated serum cortisol and ACTH levels. Differences in POMC concentration may indicate the involvement and/or impairment of central nervous system structures in hormonal alterations in FASD individuals, caused by prenatal alcohol exposure. Hormonal dysregulation in FASDs can contribute to reduced growth and development, as well as many other disturbed processes, including neurological/neurodevelopmental dysfunctions. Further insightful studies involving a larger group of patients are needed to determine the potential impact of the measured hormones.

Serum levels of leptin, ghrelin putative peptide YY-3 in patients with fetal alcohol spectrum disorders

“…Putative peptide YY-3 and ghrelin were not correlated with any clinical parameter. Furthermore, we examined the correlations between the hormones tested and other appetite-regulating hormones, including proopiomelanocortin (POMC), Agouti-signaling protein (ASP), kisspeptin (KISS1), neuropeptide Y (NPY) and alpha-melanocyte-stimulating hormone (α-MSH), which we previously determined by us 25 , 26 . We found weak correlation with POMC: a negative for PYY (r s = − 0.289, p = 0.024) and positive for ghrelin (r s = 0.268, p = 0.042).…”

“…The POMC system, which is susceptible to ethanol influence, is also intricately linked with leptin regulation. Ethanol exposure harms POMC neurons and decreases its secretion 25 , 39 , 40 . Furthermore, some evidence indicates that leptin can regulate human adrenal function through its receptors in the hypothalamus, where it modulates the secretion of corticotropin-releasing hormone and, consequently, ACTH in the pituitary 41 .…”

“…We found a positive correlation between ghrelin and POMC, involved in energy balance and neuroendocrine function 65 . Early exposure to alcohol during pregnancy has been shown to alter the activity of the hypothalamic–pituitary–adrenal axis, increasing the risk of anxiety, depression, and alcohol-related disorders 25 , 66 , 67 . Contrary to previous findings, we did not observe a relationship between ghrelin levels and BMI or glucose levels 46 , 68 .…”

Serum Levels of Hormones Regulating Appetite in Patients with Fetal Alcohol Spectrum Disorders

“…We also found a positive association between ACTH level and ASP (R = 0.380, p = 0.022). In addition, we analyzed the correlations between the hormones tested, which revealed a strong positive association between POMC [25] and ASP (R = 0.691, p < 0.001). ASP was also negatively correlated with the level of α-MSH (R = −0.316, p = 0.013).…”

Serum Appetite-Regulating Hormone Levels in Cystic Fibrosis Patients: Influence of the Disease Severity and the Type of Bacterial Infection—A Pilot Study

“…Agouti-signaling protein (ASP) and α-melanocyte-stimulating hormone (α-MSH) are involved in skin and hair pigmentation, but they are also associated with eating behavior, energy homeostasis, and adipose tissue deposition [17][18][19]. Proopiomelanocortin (POMC) is transformed in a tissue-specific manner to produce biologically active peptides, among others, such as ACTH, α-MSH, or the opioid peptide β-endorphin that are expressed primarily in the pituitary and brain [20]. POMC-derived peptides may have the opposite effect on appetite regulation [21,22].…”