Increased neck soft tissue mass and worsening of obstructive sleep apnea after growth hormone treatment in men with abdominal obesity.

BACKGROUND: Risk factors for obstructive sleep apnea (OSA) are male gender, obesity and abnormalities in neck soft tissue mass. OSA is associated with both growth hormone (GH) excess and severe GH deficiency in adults. Adults with abdominal obesity have markedly suppressed GH secretion. AIM: To study the effect of GH treatment on OSA in abdominally obese men with impaired glucose tolerance. PATIENTS AND METHODS: Forty men with abdominal obesity and glucose intolerance were randomized in a prospective, 12-month double-blind trial to receive either GH or placebo. The treatment groups had similar BMI and waist circumference. Overnight polysomnography and computed tomography to assess muscle and fat distribution in the neck and abdomen were performed at baseline and after 12 months. RESULTS: GH treatment increased insulin-like growth-factor-1i from (mean [SD]) 168 (72) to 292 (117) microg/L, the apnea-hypopnea index from (n/h) 31 (20) to 43 (25) and oxygen-desaturation index from (n/h) 18 (14) to 29 (21) (p = 0.0001, 0.001, 0.002). Neck transverse diameter, circumference and total cross-sectional area (p = 0.007, 0.01, 0.02) increased, while abdominal visceral adipose tissue (p = 0.007) was reduced. No between-group differences in total sleep time, REM sleep, NREM sleep, and time spent in supine position were found. The Epworth sleepiness scale score was unchanged. CONCLUSIONS: GH treatment increased the severity of OSA in abdominally obese men. The possible mechanism appears to be reflected by the GH-induced increase of measures of neck volume. The present results, to some extent, argue against that low GH/IGF-I activity is a primary cause of OSA in abdominally obese men.

Weight loss after gastric bypass surgery in women is followed by a metabolically favorable decrease in 11beta-hydroxysteroid dehydrogenase 1 expression in subcutaneous adipose tissue.

BACKGROUND AND AIMS: The role of 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) in the pathogenesis of obesity has been elucidated in humans and in various rodent models. Obesity is accompanied by disturbances in glucocorticoid metabolism, circulating adipokine levels, and fatty acid (FA) reesterification. This study was undertaken to evaluate glucocorticoid metabolism in sc fat before and after weight loss and to explore putative associations between 11beta-HSD1 and leptin, adiponectin, and FA recycling. SUBJECTS AND METHODS: Twenty-seven obese (mean body mass index 44.4 + or - 4.4 kg/m(2)) women underwent gastric bypass surgery. Subcutaneous fat biopsies were collected before and 2 yr after surgery. The expression of 11beta-HSD1, leptin, adiponectin, and phosphoenolpyruvate carboxykinase (PEPCK) mRNA was evaluated with real-time PCR. Serum leptin and adiponectin protein levels were estimated by ELISA. RESULTS: Two years after gastric bypass surgery, significant reductions were observed in the mean body mass index (from 44.4 to 30.8 kg/m(2)) and mean waist circumference (from 121.9 to 90.6 cm). After weight loss, 11beta-HSD1 mRNA expression decreased 4-fold (P < 0.001). Both leptin and adiponectin mRNA expression decreased, with concomitantly decreased circulating leptin and increased circulating adiponectin levels. PEPCK mRNA expression did not change. CONCLUSION: Weight loss after gastric bypass surgery was followed by metabolically favorable changes in insulin sensitivity, circulating leptin and adiponectin, and peripheral glucocorticoid metabolism. A significant reduction in 11beta-HSD1 expression was observed in sc adipose tissue after weight loss. This suggests that up-regulation of 11beta-HSD1 is a consequence, rather than a cause, of obesity.

Obesity is accompanied by disturbances in peripheral glucocorticoid metabolism and changes in FA recycling.

The glucocorticoid activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is of major interest in obesity-related morbidity. Alterations in tissue-specific cortisol levels may influence lipogenetic and gluco/glyceroneogenetic pathways in fat and liver. We analyzed the expression and activity of 11betaHSD1 as well as the expression of phosphoenolpyruvate carboxykinase (PEPCK), sterol regulatory element binding protein (SREBP), and fatty acid synthase (FAS) in adipose and liver and investigated putative associations between 11betaHSD1 and energy metabolism genes. A total of 33 obese women (mean BMI 44.6) undergoing gastric bypass surgery were enrolled. Subcutaneous adipose tissue (SAT), omental fat (omental adipose tissue (OmAT)), and liver biopsies were collected during the surgery. 11betaHSD1 gene expression was higher in SAT vs. OmAT (P = 0.013), whereas the activity was higher in OmAT (P = 0.009). The SAT 11betaHSD1 correlated with waist circumference (P = 0.045) and was an independent predictor for the OmAT area in a linear regression model. Energy metabolism genes had AT depot-specific expression; higher leptin and SREBP in SAT than OmAT, but higher PEPCK in OmAT than SAT. The expression of 11betaHSD1 correlated with PEPCK in both AT depots (P = 0.05 for SAT and P = 0.0001 for OmAT). Hepatic 11betaHSD1 activity correlated negatively with abdominal adipose area (P = 0.002) and expression positively with PEPCK (P = 0.003). In human obesity, glucocorticoid regeneration in the SAT is associated with central fat accumulation indicating that the importance of this specific fat depot is underestimated. Central fat accumulation is negatively associated with hepatic 11betaHSD1 activity. A disturbance in peripheral glucocorticoid metabolism is associated with changes in genes involved in fatty acid (FA) recycling in adipose tissue (AT).

Pubertal timing is an independent predictor of central adiposity in young adult males: the Gothenburg osteoporosis and obesity determinants study.

The role of puberty and normal variations in pubertal timing for the development of obesity in men is unclear. The aim of the current study was to investigate the impact of pubertal timing and prepubertal BMI (kg/m(2)) for young adult BMI and fat mass distribution. Detailed growth charts from birth to age 18-20 years were retrieved for the men participating in the population-based Gothenburg Osteoporosis and Obesity Determinants study. Age at peak height velocity (PHV) and BMI at age 10 years were estimated for 579 subjects, and PHV was used as an assessment of pubertal timing. The fat mass characterization and distribution were analyzed using dual X-ray absorptiometry and peripheral as well as abdominal computed tomography at age 18.9 +/- 0.5 years. We demonstrate that age at PHV is an independent negative predictor of young adult BMI and whole-body fat mass. Interestingly, age at PHV is an independent negative predictor of central, but not peripheral, fat mass. In contrast, BMI at 10 years of age predicts both central and peripheral subcutaneous fat mass. In conclusion, we demonstrate that early pubertal onset specifically predicts a central fat mass distribution, while a predominantly subcutaneous obese phenotype is strongly predicted by a high prepubertal BMI.

Whole-body T1 mapping improves the definition of adipose tissue: consequences for automated image analysis.

PURPOSE: To determine whether a whole-body T1-mapping acquisition method improves the definition of adipose tissue (AT) and simplifies automated AT segmentation compared to an image-based method. MATERIALS AND METHODS: The study included 10 subjects. Two whole-body volumes were acquired from each subject using two different flip angles. Whole-body T1 maps were calculated from each pair of whole-body volumes. AT was automatically segmented from the T1 maps and from the original image slices. The results were evaluated using manually segmented slices as reference. RESULTS: The T1-mapping method segmented more of the reference AT than the image-based method, with mean values (standard deviations (SDs)) of 87.7(5.1)% and 81.1(5.2)%, respectively. Compared to the image-based method, the T1-mapping method gives better histogram separation of AT in whole-body volumes. The suggested method also provides an output with smaller in-slice AT intensity variations. CONCLUSION: The T1-mapping method improves the definition of AT. T1-based analysis is superior to analysis based on the original images, and allows fully automated and accurate whole-body AT segmentation.