Michailidou Zoi, Jensen Michael D, Dumesic Daniel A, Chapman Karen E, Seckl Jonathan R, Walker Brian R, Morton Nicholas M
Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
Obesity (Silver Spring). 2007 May;15(5):1155-63. doi: 10.1038/oby.2007.618.
In ideopathic obesity, there is evidence that enhanced cortisol regeneration within abdominal subcutaneous adipose tissue may contribute to adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), or glucocorticoid receptor (GRalpha) levels are altered in other adipose depots remains uncertain. Our objective was to determine the association between 11betaHSD1 and GRalpha mRNA levels in four distinct adipose depots and measures of obesity and the metabolic syndrome.
Adipose tissue biopsies were collected from subcutaneous (abdominal, thigh, gluteal) and intra-abdominal (omental) adipose depots from 21 women. 11betaHSD1 and GRalpha mRNA levels were measured by real-time polymerase chain reaction. Body composition, fat distribution, fat cell size, and blood lipid, glucose, and insulin levels were measured.
11betaHSD1 mRNA was highest in abdominal subcutaneous (p < 0.001) and omental (p < 0.001) depots and was positively correlated with BMI and visceral adiposity in all depots. Omental 11betaHSD1 correlated with percent body fat (R = 0.462, p < 0.05), fat cell size (R = 0.72, p < 0.001), and plasma triglycerides (R = 0.46, p < 0.05). Conversely, GRalpha mRNA was highest in omental fat (p < 0.001). GRalpha mRNA was negatively correlated with BMI in the abdominal subcutaneous (R = -0.589, p < 0.05) and omental depots (R = -0.627, p < 0.05). Omental GRalpha mRNA was inversely associated with visceral adiposity (R = -0.507, p < 0.05), fat cell size (R = -0.52, p < 0.01), and triglycerides (R = -0.50, p < 0.05).
Obesity was associated with elevated 11betaHSD1 mRNA in all adipose compartments. GRalpha mRNA is reduced in the omental depot with obesity. The novel correlation of 11betaHSD1 with omental fat cell size, independent of obesity, suggests that intracellular cortisol regeneration is a strong predictor of hypertrophy in the omentum.
在特发性肥胖中，有证据表明腹部皮下脂肪组织中皮质醇再生增强可能导致肥胖和代谢性疾病。其他脂肪储存部位的皮质醇再生酶11β-羟基类固醇脱氢酶1型（11βHSD1）或糖皮质激素受体（GRα）水平是否改变仍不确定。我们的目的是确定四个不同脂肪储存部位的11βHSD1和GRα mRNA水平与肥胖及代谢综合征指标之间的关联。
从21名女性的皮下（腹部、大腿、臀部）和腹内（网膜）脂肪储存部位采集脂肪组织活检样本。通过实时聚合酶链反应测量11βHSD1和GRα mRNA水平。测量身体成分、脂肪分布、脂肪细胞大小以及血脂、血糖和胰岛素水平。
11βHSD1 mRNA在腹部皮下（p < 0.001）和网膜（p < 0.001）储存部位最高，且在所有储存部位均与BMI和内脏肥胖呈正相关。网膜11βHSD1与体脂百分比（R = 0.462，p < 0.05）、脂肪细胞大小（R = 0.72，p < 0.001）和血浆甘油三酯（R = 0.46，p < 0.05）相关。相反，GRα mRNA在网膜脂肪中最高（p < 0.001）。GRα mRNA在腹部皮下（R = -0.589，p < 0.05）和网膜储存部位与BMI呈负相关（R = -0.627，p < 0.05）。网膜GRα mRNA与内脏肥胖（R = -0.507，p < 0.05）、脂肪细胞大小（R = -0.52，p < 0.01）和甘油三酯（R = -0.50，p < 0.05）呈负相关。
肥胖与所有脂肪组织中11βHSD1 mRNA升高有关。肥胖时网膜储存部位的GRα mRNA减少。11βHSD1与网膜脂肪细胞大小的新关联独立于肥胖，表明细胞内皮质醇再生是网膜肥大的有力预测指标。
