Sleeve Gastrectomy Leads to Weight Loss in the Magel2 Knockout Mouse

Background Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia, obesity, cardiopulmonary diseases, and increased mortality. Although successful weight loss improves health in PWS, few treatments cause sustained weight loss in obese patients let alone obese individuals with PWS. Objectives The present study uses the Magel2 knockout (KO) mouse, an animal model of PWS, to conduct a preclinical study on the efficacy of sleeve gastrectomy(SG) in PWS. Setting Academic research laboratory, United States. Methods We performed sham or SG surgeries in 24- to 28-week-old male Magel2 KO and wild-type littermate control mice (WT) who had been maintained on a high-fat diet for 10 weeks. We monitored weight, food intake, and fat and lean mass pre- and postoperatively. Fasting glucose, glucose tolerance, and counter-regulation were measured postoperatively. Results Magel2 KO animals had similar recovery and mortality rates compared with WT. SG resulted in similar weight loss, specifically loss of fat but not lean mass, in both Magel2 KO and WT mice. SG also resulted in significantly lower fasting glucose levels and a reduction in fat intake in both Magel2 KO and WT mice. We also found that Magel2 KO mice failed to increase their food intake in response to the glucoprivic agent 2-deoxy-D-glucose, suggesting impaired glucose counter-regulation, but this occurred regardless of surgical status. All results were considered significant when P\u3c .05. Conclusion We find in this mouse model of PWS, SG is a well-tolerated, effective strategy for weight and fat loss

The Melanocortin-4 Receptor Integrates Circadian Light Cues and Metabolism

The melanocortin system directs diverse physiological functions from coat color to body weight homoeostasis. A commonality among melanocortin-mediated processes is that many animals modulate similar processes on a circannual basis in response to longer, summer days, suggesting an underlying link between circadian biology and the melanocortin system. Despite key neuroanatomical substrates shared by both circadian and melanocortin-signaling pathways, little is known about the relationship between the two. Here we identify a link between circadian disruption and the control of glucose homeostasis mediated through the melanocortin-4 receptor (Mc4r). Mc4r-deficient mice exhibit exaggerated circadian fluctuations in baseline blood glucose and glucose tolerance. Interestingly, exposure to lighting conditions that disrupt circadian rhythms improve their glucose tolerance. This improvement occurs through an increase in glucose clearance by skeletal muscle and is food intake and body weight independent. Restoring Mc4r expression to the paraventricular nucleus prevents the improvement in glucose tolerance, supporting a role for the paraventricular nucleus in the integration of circadian light cues and metabolism. Altogether these data suggest that Mc4r signaling plays a protective role in minimizing glucose fluctuations due to circadian rhythms and environmental light cues and demonstrate a previously undiscovered connection between circadian biology and glucose metabolism mediated through the melanocortin system

Bariatric surgery emphasizes biological sex differences in rodent hepatic lipid handling

Abstract Background Eighty percent of patients who receive bariatric surgery are women, yet the majority of preclinical studies are in male rodents. Because sex differences drive hepatic gene expression and overall lipid metabolism, we sought to determine whether sex differences were also apparent in these endpoints in response to bariatric surgery. Methods Two cohorts of age-matched virgin male and female Long-Evans rats were placed on a high fat diet for 3 weeks and then received either Sham or vertical sleeve gastrectomy (VSG), a surgery which resects 80% of the stomach with no intestinal rearrangement. Results Each sex exhibited significantly decreased body weight due to a reduction in fat mass relative to Sham controls (p < 0.05). Microarray and follow-up qPCR on liver revealed striking sex differences in gene expression after VSG that reflected a down-regulation of hepatic lipid metabolism and an up-regulation of hepatic inflammatory pathways in females vs. males after VSG. While the males had a significant reduction in hepatic lipids after VSG, there was no reduction in females. Ad lib-fed and fasting circulating triglycerides, and postprandial chylomicron production were significantly lower in VSG relative to Sham animals of both sexes (p < 0.01). However, hepatic VLDL production, highest in sham-operated females, was significantly reduced by VSG in females but not males. Conclusions Taken together, although both males and females lose weight and improve plasma lipids, there are large-scale sex differences in hepatic gene expression and consequently hepatic lipid metabolism after VSG.http://deepblue.lib.umich.edu/bitstream/2027.42/135948/1/13293_2017_Article_126.pd

Participatory Process for Implementing a Colorectal Cancer Screening Intervention: an Action Plan for Local Sustainability

Background: Rigid protocols can hamper translation of evidence-based interventions from research to real-world settings. This investigation aimed to develop procedures for modifying the study protocol of a community-based participatory research (CBPR) project and to analyze the theoretical constructs that underlie this process. Methods: The research project is a dissemination and implementation study of the Educational Program to Increase Colorectal Cancer Screening (EPICS), an evidence-based intervention targeting African Americans in the United States. The study is being conducted in a partnership with community coalitions in 15 different cities. Each site initially presented unique issues that required modification of the study protocol. Results: In order to honor underlying CBPR theory, it was necessary to negotiate protocol changes with the community coalition at each site, while insuring preservation of the core elements of the intervention. Conclusions: We discuss the ways in which this represents a narrowing of the gap between CBPR and traditional research approaches

UV Circular Polarisation in Star Formation Regions : The Origin of Homochirality?

Ultraviolet circularly polarised light has been suggested as the initial cause of the homochirality of organic molecules in terrestrial organisms, via enantiomeric selection of prebiotic molecules by asymmetric photolysis. We present a theoretical investigation of mechanisms by which ultraviolet circular polarisation may be produced in star formation regions. In the scenarios considered here, light scattering produces only a small percentage of net circular polarisation at any point in space, due to the forward throwing nature of the phase function in the ultraviolet. By contrast, dichroic extinction can produce a fairly high percentage of net circular polarisation (∼10%) and may therefore play a key role in producing an enantiomeric excessPeer reviewe

Additional file 1: Figure S1. of Bariatric surgery emphasizes biological sex differences in rodent hepatic lipid handling

Hepatic gene changes in females following VSG and sham surgeries. Gray bars designate categories that were down-regulated in VSG. Black bars designate genes that were up-regulated in VSG. B. Gene lists for categories of gene changes exhibited in panel A (n = 3/group). (PDF 112 kb