In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show "browning" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic.

No abstract

al., 1992). In contrast to the many reports of extragonadal germ cell tumours, there have been only a few reports of testicular tumours (Carroll et al., 1988;Dexeus et al., 1988;Reddy et al., 1991).No September 1994 cinoma of the breast were observed. which was similar to the expected incidence in women (Price et al.. 1985).The many case reports of KS and cancer are suggestive of a relationship. but do not allow any estimates of the relative risk of cancer in men with KS. Such data are important to help in prenatal counselling and to physicians who take care of patients with KS. This study presents the cancer incidence in a large cohort of men with KS with a virtually complete follow-up. Materials and methodsThe stud) cohort The Danish Cytogenetic Register was founded in 1968 and has collected information on chromosomal abnormalities diagnosed in Denmark (Nielsen. 1980). The register is based upon reports from seven cytogenetic laboratories throughout the country. It is assumed that the register has a virtually complete coverage of the constitutional chromosomal abnormalities diagnosed in Denmark since 1961.A total of 707 men with a diagnosis of KS were registered in the Cytogenetic Register by December 1992. Two persons were not Danish residents and were excluded from the cohort. Two persons were excluded because of insufficient follow-up data. Six persons were excluded because of an additonal somatic trisomy (five with trisomy 18 and one with trisomy 21). One of the prenatally diagnosed patients had a twin brother with normal karyotype and had to be excluded from the study because the case person could not be identified. Accordingly, the final study cohort consisted of 696 men with KS, of whom 20 were diagnosed prenatally.

ObjectiveA disturbed day-night rhythm is associated with metabolic perturbations that can lead to obesity and type 2 diabetes mellitus (T2DM). In skeletal muscle, a reduced oxidative capacity is also associated with the development of T2DM. However, whether oxidative capacity in skeletal muscle displays a day-night rhythm in humans has so far not been investigated.MethodsLean, healthy subjects were enrolled in a standardized living protocol with regular meals, physical activity and sleep to reflect our everyday lifestyle. Mitochondrial oxidative capacity was examined in skeletal muscle biopsies taken at five time points within a 24-hour period.ResultsCore-body temperature was lower during the early night, confirming a normal day-night rhythm. Skeletal muscle oxidative capacity demonstrated a robust day-night rhythm, with a significant time effect in ADP-stimulated respiration (state 3 MO, state 3 MOG and state 3 MOGS, p < 0.05). Respiration was lowest at 1 PM and highest at 11 PM (state 3 MOGS: 80.6 ± 4.0 vs. 95.8 ± 4.7 pmol/mg/s). Interestingly, the fluctuation in mitochondrial function was also observed in whole-body energy expenditure, with peak energy expenditure at 11 PM and lowest energy expenditure at 4 AM (p < 0.001). In addition, we demonstrate rhythmicity in mRNA expression of molecular clock genes in human skeletal muscle.ConclusionsOur results suggest that the biological clock drives robust rhythms in human skeletal muscle oxidative metabolism. It is tempting to speculate that disruption of these rhythms contribute to the deterioration of metabolic health associated with circadian misalignment.