Thomas Reinehr, Alberto Sánchez-Guijo, Nina Lass and Stefan A Wudy
Little information is available on the steroid sulfates profile in obese children. Therefore, we examined whether sulfated steroids are linked with weight status and associated comorbidities in obese children.
We analyzed 66 obese children (mean age 10.5 ± 2.5 years, 57.6% female, 53.9% prepubertal, mean BMI 27.0 ± 4.6 kg/m2, 50% with BMI-SDS reduction >0.5, 50% without BMI-SDS reduction) who participated in an outpatient 1-year intervention program based on exercise, behavior and nutrition therapy. We measured intact sulfated steroids (cholesterol sulfate (CS), pregnenolone sulfate (PregS), 17αOH pregnenolone sulfate (17OH-PregS), 16αOH dehydroepiandrosterone sulfate (16OH-DHEAS), DHEAS, androstenediol-3-sulfate, androsterone sulfate and epiandrosterone sulfate) by LC–MS/MS, and insulin resistance index HOMA, lipids, blood pressure at baseline and 1 year later.
All sulfated steroids except 17OH-PregS, 16OH-DHEAS, androsterone sulfate and epiandrosterone sulfate were higher in boys compared to girls. Concentrations of CS before intervention were higher in children who lost weight. After 1 year of treatment, both groups showed increased levels of DHEAS, 16OH-DHEAS and androstenediol-3-sulfate, but PregS was only increased in children with weight loss. None of the steroid sulfates was significantly related to cardiovascular risk factors or HOMA except 17OH-PregS, which was associated with systolic blood pressure both in cross-sectional (β-coefficient: 0.09 ± 0.07, P = 0.020) and longitudinal analyses (β-coefficient: 0.06 ± 0.04, P = 0.013) in multiple linear regression analyses.
Since higher steroid sulfation capacity was associated with successful weight intervention in children disruption of sulfation may be associated with difficulties to lose weight. Future studies are necessary to prove this hypothesis.
Aneta Gawlik, Michael Shmoish, Michaela F Hartmann, Stefan A Wudy, Zbigniew Olczak, Katarzyna Gruszczynska and Ze’ev Hochberg
Analysis of steroids by gas chromatography-mass spectrometry (GC-MS) defines a subject’s steroidal fingerprint. Here, we compare the steroidal fingerprints of obese children with or without liver disease to identify the ‘steroid metabolomic signature’ of childhood nonalcoholic fatty liver disease.
Urinary samples of 85 children aged 8.5–18.0 years with BMI >97% were quantified for 31 steroid metabolites by GC-MS. The fingerprints of 21 children with liver disease (L1) as assessed by sonographic steatosis (L1L), elevated alanine aminotransferases (L1A) or both (L1AL), were compared to 64 children without markers of liver disease (L0). The steroidal signature of the liver disease was generated as the difference in profiles of L1 against L0 groups.
L1 comparing to L0 presented higher fasting triglycerides (P = 0.004), insulin (P = 0.002), INS/GLU (P = 0.003), HOMA-IR (P = 0.002), GGTP (P = 0.006), AST/SGOT (P = 0.002), postprandial glucose (P = 0.001) and insulin (P = 0.011). L1AL showed highest level of T-cholesterol and triglycerides (P = 0.029; P = 0.044). Fasting insulin, postprandial glucose, INS/GLU and HOMA-IR were highest in L1L and L1AL (P = 0.001; P = 0.017; P = 0.001; P = 0.001). The liver disease steroidal signature was marked by lower DHEA and its metabolites, higher glucocorticoids (mostly tetrahydrocortisone) and lower mineralocorticoid metabolites than L0. L1 patients showed higher 5α-reductase and 21-hydroxylase activity (the highest in L1A and L1AL) and lower activity of 11βHSD1 than L0 (P = 0.041, P = 0.009, P = 0.019).
The ‘steroid metabolomic signature’ of liver disease in childhood obesity provides a new approach to the diagnosis and further understanding of its metabolic consequences. It reflects the derangements of steroid metabolism in NAFLD that includes enhanced glucocorticoids and deranged androgens and mineralocorticoids.