Deletion of Rptor in preosteoblasts reveals a role for the mammalian target of rapamycin complex 1 (mTORC1) complex in dietary-induced changes to bone mass and glucose homeostasis in female mice

The mammalian target of rapamycin complex 1 (mTORC1) complex is the major nutrient sensor in mammalian cells that responds to amino acids, energy levels, growth factors, and hormones, such as insulin, to control anabolic and catabolic processes. We have recently shown that suppression of the mTORC1 complex in bone-forming osteoblasts (OBs) improved glucose handling in male mice fed a normal or obesogenic diet. Mechanistically, this occurs, at least in part, by increasing OB insulin sensitivity leading to upregula- tion of glucose uptake and glycolysis. Given previously reported sex-dependent differences observed upon antagonism of mTORC1 signaling, we investigated the metabolic and skeletal effects of genetic inactivation of preosteoblastic-mTORC1 in female mice. Eight- week-old control diet (CD)-fed Rptor ob −/− mice had a low bone mass with a significant reduction in trabecular bone volume and trabecular number, reduced cortical bone thickness, and increased marrow adiposity. Despite no changes in body composition, CD-fed Rptor ob −/− mice exhibited significant lower fasting insulin and glucose levels and increased insulin sensitivity. Upon high-fat diet (HFD) feeding, Rptor ob −/− mice were resistant to a diet-induced increase in whole-body and total fat mass and protected from the development of diet-induced insulin resistance. Notably, although 12 weeks of HFD increased marrow adiposity, with minimal changes in both trabecular and cortical bone in the female control mice, marrow adiposity was significantly reduced in HFD-fed Rptor ob −/− compared to both HFD-fed control and CD-fed Rptor ob −/− mice. Collectively, our results demonstrate that mTORC1 func- tion in preosteoblasts is crucial for skeletal development and skeletal regulation of glucose homeostasis in both male and female mice. Importantly, loss of mTORC1 function in OBs results in metabolic and physiological adaptations that mirror a caloric restriction phenotype (under CD) and protects against HFD-induced obesity, associated insulin resistance, and marrow adiposity expansion. These results highlight the critical contribution of the skeleton in the regulation of whole-body energy homeostasisPawanrat Tangseefa, Sally K. Martin, Agnieszka Arthur, Vasilios Panagopoulos, Amanda J. Page, Gary A. Wittert ... et al

Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?

Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control