Department of Pediatrics, Inje University Sanggye Paik Hospital, Seoul, 01757, South Korea.
Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul, 02792, South Korea.
Mol Cell Endocrinol. 2021 May 1;527:111225. doi: 10.1016/j.mce.2021.111225. Epub 2021 Feb 26.
Dysregulation of glucocorticoid metabolism is known to be a causative factor of obesity. However, only a few studies have evaluated the enzymatic activities involved in glucocorticoid metabolism in the pediatric population.
To examine whether circulating glucocorticoid metabolites and their ratios reflecting the activities of metabolic enzyme are associated with obesity and body composition in girls.
A total of 227 girls aged 7-13 years (131 control, 45 overweight, 51 obese) were enrolled in this study. Serum concentrations of glucocorticoids (11-deoxycortisol, cortisol, tetrahydrocortisol [THF], allo-THF, allo-dihydrocortisol [allo-DHF], and cortisone) were evaluated by gas chromatography-mass spectrometry. Enzyme activities corresponding to the ratios of cortisol and cortisone to their respective precursors and metabolites were also assessed.
Serum levels of allo-THF were significantly higher in obese girls compared with those in overweight and control girls (P = 0.018); however, concentrations of other cortisol metabolites were not significantly different between the groups studied. According to the severity of obesity, increasing trends in the metabolic ratios reflecting the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) [(cortisol + allo-DHF + allo-THF + THF)/cortisone], relative 5α/5β-reductase [allo-THF/THF] activity, and 3α-HSD [allo-THF/allo-DHF] activity, were noted (P-for-trend <0.05). Body fat percentage and waist-to-height ratio positively correlated with the activities of 11β-HSD1 and 3α-HSD (P < 0.05). Following covariate control, girls with central obesity demonstrated significantly higher metabolic ratios reflecting 11β-HSD1, relative 5α/5β-reductase, and 3α-HSD activities (P < 0.05).
We found an altered glucocorticoid metabolism suggesting increased production of cortisol by 11β-HSD1 and increased metabolic clearance of cortisol catalyzed by 3α-HSD in girls with central obesity.
糖皮质激素代谢失调已被证实是肥胖的一个致病因素。然而，仅有少数研究评估了糖皮质激素代谢相关酶的酶活性在儿科人群中的作用。
检测循环糖皮质激素代谢产物及其反映代谢酶活性的比值与女童肥胖和体成分的相关性。
共纳入 227 名年龄 7-13 岁的女童（对照组 131 名，超重组 45 名，肥胖组 51 名），采用气相色谱-质谱法检测血清中糖皮质激素（11-脱氧皮质醇、皮质醇、四氢皮质醇[THF]、差向-THF、差向-二氢皮质醇[allo-DHF]和皮质酮）的浓度。同时还评估了皮质醇和皮质酮与其前体及代谢产物比值所对应的酶活性。
肥胖女童的血清差向-THF 水平显著高于超重和对照组女童（P=0.018），而其他皮质醇代谢产物的浓度在各组间无显著差异。根据肥胖严重程度，反映 11β-羟类固醇脱氢酶 1（11β-HSD1）活性的代谢比值[（皮质醇+allo-DHF+差向-THF+THF）/皮质酮]、相对 5α/5β-还原酶[差向-THF/THF]活性和 3α-HSD[差向-THF/allo-DHF]活性呈逐渐升高趋势（P-for-trend<0.05）。体脂肪百分比和腰高比与 11β-HSD1 和 3α-HSD 的活性呈正相关（P<0.05）。校正协变量后，中心性肥胖女童的代谢比值反映 11β-HSD1、相对 5α/5β-还原酶和 3α-HSD 活性更高（P<0.05）。
我们发现糖皮质激素代谢发生改变，提示中心性肥胖女童的 11β-HSD1 活性增强，皮质醇生成增加，3α-HSD 催化的皮质醇代谢清除率增加。
