Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 690, Hôpital Robert Debré, Université Paris 7 Denis Diderot, 48 Boulevard Sérurier, Paris FR-75019, France.
J Clin Endocrinol Metab. 2010 Aug;95(8):3949-54. doi: 10.1210/jc.2010-0254. Epub 2010 Jun 2.
The mechanisms relating being born small for gestational age (SGA) and the later risk of metabolic disorders are not yet fully understood. Adipose 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity and expression have been positively associated with metabolic syndrome. In humans, no in vivo studies have explored 11beta-HSD1 activity and gene expression in sc adipose tissue of SGA subjects.
Thirty-nine subjects SGA (birth weight<10th percentile) were matched on gender and age with 36 subjects born appropriate for gestational age (AGA) (25th percentile<birth weight<75th percentile); the two groups were stratified according to body fat content into low-fat-mass (20 SGA and 18 AGA) and high-fat-mass (19 SGA and 18 AGA) subjects. Basal and stimulated activities of the 11beta-HSD1 enzyme were assessed in the effluent of microdialysis performed in the abdominal sc wall in vivo. mRNA expression was measured by real-time quantitative PCR.
Basal 11beta-HSD1 activity was comparable in both groups, whereas stimulated activity was lower in SGA subjects. A significant effect of body fat content on the stimulated 11beta-HSD1 activity was found in AGA but not in SGA subjects. 11beta-HSD1 expression was associated with body fat but not with birth weight.
The in vivo stimulated 11beta-HSD1 activity was decreased in subjects born SGA as compared with adults born AGA. 11beta-HSD1 gene expression was not associated with birth weight. It is therefore unlikely that local glucocorticoid metabolism in sc fat plays a major role in the development of the metabolic complications associated with being born SGA.
对于出生体重小于胎龄（SGA）与后期代谢紊乱风险之间的关系，其机制尚不完全清楚。脂肪 11β-羟类固醇脱氢酶 1（11β-HSD1）的活性和表达与代谢综合征呈正相关。在人体中，尚无研究探索过 SGA 患者的 sc 脂肪组织中 11β-HSD1 的活性和基因表达。
本研究共纳入 39 名 SGA 受试者（出生体重<第 10 百分位数），并按照性别和年龄与 36 名 AGA 受试者（第 25 百分位数<出生体重<第 75 百分位数）进行匹配；两组根据体脂含量分为低脂肪量（20 名 SGA 和 18 名 AGA）和高脂肪量（19 名 SGA 和 18 名 AGA）组。通过在体内进行腹部 sc 壁微透析，评估 11β-HSD1 酶的基础和刺激活性。通过实时定量 PCR 测量 mRNA 表达。
两组的基础 11β-HSD1 活性相当，而 SGA 组的刺激活性较低。在 AGA 组中，体脂含量对刺激 11β-HSD1 活性有显著影响，但在 SGA 组中没有影响。11β-HSD1 的表达与体脂有关，而与出生体重无关。
与 AGA 出生的成年人相比，SGA 出生的受试者体内刺激的 11β-HSD1 活性降低。11β-HSD1 基因表达与出生体重无关。因此，局部 sc 脂肪中的糖皮质激素代谢不太可能在与 SGA 相关的代谢并发症的发展中起主要作用。
