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The concentration of serum testosterone is mainly regulated by the testicular function, which is under control of the central hypothalamic-pituitary-gonadal axis. A certain amount of testosterone is converted into beta-estradiol by adipose tissue. Obesity in men is often associated with decreased androgen levels. The aim of the present study was to examine the effect of caloric restriction on serum testosterone levels in obese men. Dietary intervention study was performed with a very low calorie diet (800 kcal/d) for 12 weeks. Thirteen obese human male subjects (median body mass index: 42.7 kg/m(2)) were included. Body composition was assessed by impedance analysis. Insulin sensitivity was estimated by leptin-to-adiponectin ratio (LAR). Testosterone (T), beta-estradiol, albumin, sex hormone-binding globulin (SHBG), LH, and FSH serum concentrations were measured by enzyme immunoassays. Statistical analysis was performed on baseline and values after 3 months. Caloric restriction significantly increased total testosterone (6.97 nmol/l to 13.21 nmol/l; p = 0.001) and SHBG (22.11 nmol/l to 42.12 nmol/l; p = 0.001) concentrations in serum. This is caused by a significant improvement of the testicular function (LH/T: 0.36-0.20; p = 0.005) and a significant reduction of the T/beta-estradiol conversion rate (73.59-104.29; p = 0.003). There was a signifi cant negative correlation of improvement of testicular function and LAR (r(s) = -0.683 (p = 0.042)). In obese men caloric restriction significantly increases the serum testosterone concentration. This is achieved by 2 distinct mechanisms, that is, improvement of testicular function and reduced conversion of testosterone to beta-estradiol by aromatase activity of the adipose tissue.

The use of thyroid-stimulating hormone (TSH) testing in routine laboratory screening and testing of TSH before administration of contrast medium, resulted in an increased number of incidentally detected elevated TSH levels. In the case of slightly increased values in asymptomatic patients, repeated measurement of TSH is recommended for confirmation. Confirmed elevated TSH levels should lead to additional measurements of the peripheral thyroid hormones, determination of thyroid autoantibodies and performance of thyroid gland ultrasound examination. The most common reasons for acquired subclinical and overt hypothyroidism are autoimmune diseases of the thyroid gland and in many cases substitution therapy with levothyroxine is then necessary. In subclinical hypothyroidism it remains unclear at which TSH levels the initiation of substitution therapy makes sense. In the case of simultaneously elevated peripheral thyroid hormones rare diseases, such as secondary hyperthyroidism and thyroid hormone resistance should be considered.

In patients with obesity and type 2 diabetes, adipose tissue is infiltrated by macrophages known to alter adipogenesis of mesenchymal precursor cells via secretion of proinflammatory cytokines. Recently, it has been shown that under certain conditions, immune cells can also express wnt-5a, a factor known to inhibit adipogenesis in humans. Therefore, in this study we aimed to investigate whether macrophages affect adipogenesis of mesenchymal precursor cells via wnt-5a. Wnt-5a was found to be expressed in adipose tissue macrophages in obese and type 2 diabetic human subjects in vivo by immunohistochemistry of adipose tissue biopsies. Furthermore, wnt-5a was detectable in circulating CD14(+) blood monocytes of human subjects with obesity and type 2 diabetes on RNA level by real-time PCR. Besides expression analysis in vivo, we also performed functional studies to explore the role of wnt-5a in low-grade inflammation of adipose tissue. In a cell culture experiment, macrophage-conditioned differentiation medium inhibited adipogenesis of 3T3-L1 cells. This inhibitory effect was restored by adding neutralising anti-wnt-5a antibodies. In conclusion, our data indicate that macrophages alter adipogenesis of 3T3-L1 cells not only via classical proinflammatory cytokines, but also via wnt signalling molecules. International Journal of Obesity (2011) 35, 1450-1454; doi:10.1038/ijo.2011.6; published online 1 February 2011

AIMS: The predominance of small dense low-density lipoproteins (sdLDLs) has been associated with increased cardiovascular risk. The effect of ezetimibe on LDL subfraction distribution has not been fully elucidated. This study assessed by gradient gel electrophoresis the effects of ezetimibe alone, simvastatin alone, and their combination on sdLDL subfraction distribution. METHODS AND RESULTS: A single-centre, randomized, parallel three-group open-label study was performed in 72 healthy men with a baseline LDL-cholesterol (LDL-C) concentration of 111 +/- 30 mg/dL (2.9 +/- 0.8 mmol/L). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24), or their combination (n = 24) for 14 days. Blood was drawn before and after the treatment period. Generalized estimating equations were used to assess the influence of drug therapy on LDL subfraction distribution, controlling for within-subject patterns (clustering). We adjusted for age, body mass index, and baseline concentrations of LDL-C and triglycerides. Ezetimibe alone changed LDL subfraction distribution towards a more atherogenic profile by significantly increasing sdLDL subfractions (LDL-IVA +14.2%, P = 0.0216 and LDL-IVB +16.7%, P = 0.039; fully adjusted Wald chi(2) test). In contrast, simvastatin alone significantly decreased the LDL-IVB subfraction (-16.7%, P = 0.002). This effect was offset when simvastatin was combined with ezetimibe (LDL-IVB +14.3%, P = 0.44). All three treatments decreased the large, more buoyant LDL-I subfraction, the effects of ezetimibe being the most pronounced (ezetimibe -13.9%, P < 0.0001; combination therapy -7.3%, P = 0.0743; simvastatin -4.6%, P < 0.0001). CONCLUSION: In healthy men, treatment with ezetimibe alone is associated with the development of a pro-atherogenic LDL subfraction profile. Potentially atheroprotective effects of simvastatin are offset by ezetimibe. This study is registered with ClinicalTrials.gov, identifier no. NCT00317993.