Restructuring of the male mice peripheral circadian network after bariatric surgery

Bariatric surgery is still the most effective long-term weight-loss therapy. Recent data indicate that surgical outcomes may be affected by diurnal food intake patterns. In this study, we aimed to investigate how surgery-induced metabolic adaptations (i.e. weight loss) interact with circadian clock function. For that reason, vertical sleeve gastrectomy (VSG) was performed in obese mice and rhythms in behavior, tissue rhythmicity, and white adipose tissue transcriptome were evaluated. VSG under constant darkness conditions led to a maximum weight loss of 18 % compared to a loss of 3 % after sham surgery. Post-surgical weight development was characterized by two distinct intervals of catabolic and subsequent anabolic metabolic state. Locomotor activity was not affected. However, VSG significantly increased active phase meal frequency in the anabolic state. No significant effects on clock gene rhythmicity were detected in adrenal and white adipose tissue (WAT) explant cultures. Transcriptome rhythm analyses of subcutaneous WAT revealed a reduction of cycling genes after VSG (sham: 2,493 vs. VSG: 1,013) independent of sustained rhythms in core clock gene expression. This may be a consequence of weight loss-induced morphological reconstruction of WAT that overwrites the direct influence of the local clock machinery on the transcriptome. However, VSG altered rhythmic transcriptional regulation of WAT lipid metabolism pathways. Thus, our data suggest a reorganization of diurnal metabolic rhythms after VSG downstream of the molecular clock machinery.

Effects of magnitude of visceral adipose tissue reduction: Impact on insulin resistance, hyperleptinemia and cardiometabolic risk in adolescents with obesity after long-term weight-loss therapy

Aim: To investigate the association between visceral adipose tissue loss and insulin resistance and hyperleptinemia in adolescents with obesity submitted to interdisciplinary weight-loss therapy. Methods: A total of 172 post-pubertal adolescents (body mass index greater than the 95th percentile of the Centers for Disease Control and Prevention reference growth charts) were recruited for the study. The adolescents were assigned to long-term weight-loss therapy. Body composition, visceral and subcutaneous fat, glucose metabolism, lipid profile, hepatic enzymes and leptin concentration were measured. After the therapy, the adolescents were allocated to three different groups according to the tertile of visceral fat reduction. Results: Positive effects on body composition were observed in all analysed groups independent of visceral fat reduction. It was found that visceral fat was an independent predictor of insulin resistance in the investigated population. Obese adolescents who lost a higher proportion of visceral adipose tissue (>1.8 cm) demonstrated improved metabolic and inflammatory parameters twice as much than those who presented smaller losses. Positive correlations between visceral fat reduction and glucose metabolism, lipid profile, hepatic enzymes and homeostasis model assessment of insulin resistance index were demonstrated. Conclusion: The magnitude of the reduction in visceral fat was an independent predictor of insulin resistance, hyperleptinemia and metabolic disorders related to obese adolescents.