The sexual dimorphism in human body fat distribution suggests a causal role for sex hormones. This is of particular importance when considering the role of excess visceral adipose tissue accumulation as a critical determinant of obesity-related cardiometabolic alterations. Scientific literature on the modulation of body fat distribution by androgens in humans is abundant, remarkably inconsistent and difficult to summarize. We reviewed relevant literature on this topic, with a particular emphasis on androgen replacement, androgen effects on selected parameters of adipose tissue function and adipose tissue steroid-converting enzymes. In men, low androgenic status mostly reflected by reduced total testosterone is a frequent feature of visceral obesity and the metabolic syndrome. Regarding testosterone therapy, however, studies must be appreciated in the context of current controversies on their cardiovascular effects. Analyses of available studies suggest that decreases in waist circumference in response to testosterone are more likely observed in men with low levels of testosterone and high BMI at study onset. In women with androgen excess, higher testosterone and free testosterone levels are fairly consistent predictors of increased abdominal and/or visceral adipose tissue accumulation, which is not the case in nonhyperandrogenic women. Regarding mechanisms, androgens decrease adipogenesis and markers of lipid storage in vitro in men and women. Evidence also suggest that local steroid transformations by adipose tissue steroid-converting enzymes expressed in a depot-specific fashion may play a role in androgen-mediated modulation of body fat distribution. Accumulating evidence shows that androgens are critical modulators of body fat distribution in both men and women. © 2018 American Physiological Society. Compr Physiol 8:1253-1290, 2018.
Objective To investigate and further characterize the process of mature adipocyte dedifferentiation. Our hypothesis was that dedifferentiation does not involve mitosis but rather a phenomenon of liposecretion. Methods Mature adipocytes were isolated by collagenase digestion of human adipose tissue samples. Ceiling cultures were established using our six‐well plate model. Cells were treated with cytosine β‐d‐arabinofuranoside (AraC) or vincristine (VCR), two agents blocking cell division, and were compared with vehicle. Liposecretion events were visualized by time‐lapse microscopy, with and without AraC in adipocytes transducted with a baculovirus. Microscopic analyses were performed after labeling phosphorylated histone 3 and cyclin B1 in ceiling cultures. Results Treatment with AraC almost entirely prevented the formation of fibroblasts up to 12 days of ceiling culture. Similar results were obtained with VCR. The antimitotic effectiveness of the treatment was confirmed in fibroblast cultures from the adipose tissue stromal‐vascular fraction by proliferation assays and colony‐forming unit experiments. Using time‐lapse microscopy, we visualized liposecretion events in which a large lipid droplet was rapidly secreted from isolated mature adipocytes. The same phenomenon was observed with AraC. This was observed in conjunction with histone 3 phosphorylation and cyclin B1 segregation to the nucleus. Conclusion Our results support the notion that dedifferentiation involves rapid secretion of the lipid droplet by the adipocytes with concomitant generation of fibroblast‐like cells that subsequently proliferate to generate the dedifferentiated adipocyte population during ceiling culture. The presence of mitotic markers suggests that this process involves cell cycle progression, although cell division does not occur.
Background: Because of logistic challenges associated with the COVID-19 pandemic, direct oral anticoagulants (DOAC) were favored over warfarin in patients presenting postoperative atrial fibrillation (AF) after cardiac surgery in our institution. Considering the limited evidence supporting the use of DOAC in this context, we sought to evaluate the safety and efficacy of this practice change. Methods: A retrospective study was performed with patients from the Quebec City metropolitan area who were hospitalized at the Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval following cardiac surgery and who required oral anticoagulant (OAC) for postoperative AF. The primary objective was to compare the pre- and peri-COVID-19 period for OAC prescribing patterns and the incidence of thrombotic and bleeding events at 3 months post-surgery. The secondary objective was to compare DOAC to warfarin in terms of thrombotic events and bleeding events. Results: A total of 233 patients were included, 142 from the pre-COVID-19 and 91 from the peri-COVID-19 period, respectively. Both groups had equivalent proportions of preoperative AF (48%) and new-onset postoperative AF (52%). The proportion of patients treated with a DOAC increased from 13% pre-COVID-19 to 82% peri-COVID-19. This change in practice was not associated with a significant difference in the incidence of thrombotic or bleeding events 3 months postoperatively. However, compared to DOAC, warfarin was associated with a higher incidence of major bleeding. Only 1 thrombotic event was reported with warfarin, and none were reported with DOAC. Conclusion: This study suggests that DOAC are an effective and safe alternative to warfarin to treat postoperative AF after cardiac surgery and that this practice can be safely maintained.
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