Single-dose glucagon-like peptide 1 (GLP1) therapy increases postprandial plasma IL6 levels in prediabetic, obese humans. GLP1-IL6 interactions underly multiple antidiabetic effects, but these may differ after acute versus chronic therapy. This study examines postprandial effects of GLP1 after chronic therapy. Seven humans (six Black) with prediabetes and obesity completed 6 weeks of exenatide extended release therapy. Then subjects returned for pre- and post-meal measurements of plasma IL6, GLP1, glucagon, and related inflammatory markers. Weight, which was measured before and after therapy, did not change. Plasma IL6 decreased from baseline to postmeal state ( = 0.016), with decreases in free fatty acids (P < 0.001) and increases in insulin (P = 0.002), glucose (P < 0.0001), triglycerides (P = 0.0178), and glucagon (P = 0.018). Baseline GLP1 levels matched 6 weeks of therapy. The fall in postprandial plasma IL6, which contrasts with the increase after acute therapy, highlights the need for more investigation regarding the mechanisms of acute versus chronic GLP1-IL6 signaling.

This study estimates peer effects on alcohol use, drawing from a database of about 2000 randomly-assigned roommates on a college campus. The estimation of peer influences also takes into consideration ego's history of alcohol use and friendship with the peer. College students averaged an additional two-fifths of a binge drinking episode per month and an additional one-half of a drinking episode per month when randomly assigned a roommate who drank in high school than when assigned a roommate who did not drink in high school. An individual's prior history of alcohol use proves important. Peer effects on binge drinking as well as drinking for those who already drank in high school were about twice as large as average peer effects. When one did not have a history of alcohol use, negative peer influences were absent. Also important is the friendship between peers. When a peer is considered a best friend, the step-up effect (or positive interaction effect) increased by 1.25-1.61 drinking episodes per month. However, even when a peer is not considered a best friend, a drinking peer still increased ego's drinking episodes by 0.75-1.00 per month.

The authors draw data from the College Roommate Study (ROOM) and the National Longitudinal Study of Adolescent Health to investigate gene-environment interaction effects on youth binge drinking. In ROOM, the environmental influence was measured by the precollege drinking behavior of randomly assigned roommates. Random assignment safeguards against friend selection and removes the threat of gene-environment correlation that makes gene-environment interaction effects difficult to interpret. On average, being randomly assigned a drinking peer as opposed to a nondrinking peer increased college binge drinking by 0.5-1.0 episodes per month, or 20%-40% the average amount of binge drinking. However, this peer influence was found only among youths with a medium level of genetic propensity for alcohol use; those with either a low or high genetic propensity were not influenced by peer drinking. A replication of the findings is provided in data drawn from Add Health. The study shows that gene-environment interaction analysis can uncover social-contextual effects likely to be missed by traditional sociological approaches.

Mechanisms underlying anti-diabetic effects of GLP1 analogs remain incompletely understood. We observed that in prediabetic humans exenatide treatment acutely induces interleukin-6 (IL-6) secretion by monocytes and IL-6 in systemic circulation. We hypothesized that GLP1 analogs signal through IL-6 in adipose tissue (AT) and used the mouse model to test if IL-6 receptor (IL-6R) signaling underlies the effects of the GLP1-IL-6 axis. We show that liraglutide transiently increases IL-6 in mouse circulation and IL-6R signaling in AT. Metronomic liraglutide treatment resulted in AT browning and thermogenesis linked with STAT3 activation. IL-6-blocking antibody treatment inhibited STAT3 activation in AT and suppressed liraglutide-induced increase in thermogenesis and glucose utilization. We show that adipose IL-6R knockout mice still display liraglutide-induced weight loss but lack thermogenic adipocyte browning and metabolism activation. We conclude that the anti-diabetic effects of GLP1 analogs are mediated by transient upregulation of IL-6, which activates canonical IL-6R signaling and thermogenesis.

Background: The state of prediabetes comprises atherosclerotic changes leading to decreased vascular function in humans. This study examined the effects on incretin mimetics on vascular physiology in the prediabetic postprandial state. Methods: Fifteen obese adults with prediabetes participated in a randomized, crossover, double-blinded trial comparing the postprandial effects of exenatide, saxagliptin, and placebo on peripheral vasodilation. All studies utilized a standardized high-fat meal. Resting and peak forearm blood flow (FBF) were measured via strain gauge venous occlusion plethysmography, and makers of vascular dysfunction were measured in plasma. Results: Exenatide attenuated resting FBF at 3 hr (P = 0.003) and 6 hr (P = 0.056) postmeal, compared to placebo. Nonsignificant reductions in resting FBF were observed between saxagliptin and placebo at the same time points. No group differences were observed for peak FBF, plasma nitrotyrosine, and plasma 8-iso-prostaglandin F2alpha. A transient increase in plasma triglyceride was abated in the exenatide group, when compared to saxagliptin and placebo groups. Only exenatide group showed no significant upsurge in plasma insulin. Plasma-free fatty acids significantly declined in all three groups, although less markedly for exenatide. Postmeal glucose increased at 2 hr with placebo and saxagliptin, but simultaneously decreased with exenatide. Conclusions: Acute treatment with exenatide blunted the postprandial vasodilatory effect of a high-fat meal in prediabetes. Exenatides acute effects derived primarily from multiple endothelium-independent processes. Trial Registration Number: NCT02104739.

Ferromagnet/two-dimensional transition-metal dichalcogenide (FM/2D TMD) interfaces provide attractive opportunities to push magnetic information storage to the atomically thin limit. Existing work has focused on FMs contacted with mechanically exfoliated or chemically vapor-deposition-grown TMDs, where clean interfaces cannot be guaranteed. Here, we report a reliable way to achieve contamination-free interfaces between ferromagnetic CoFeB and molecular-beam epitaxial MoSe₂. We show a spin reorientation arising from the interface, leading to a perpendicular magnetic anisotropy (PMA), and reveal the CoFeB/2D MoSe₂ interface allowing for the PMA development in a broader CoFeB thickness-range than common systems such as CoFeB/MgO. Using X-ray magnetic circular dichroism analysis, we attribute generation of this PMA to interfacial d-d hybridization and deduce a general rule to enhance its magnitude. We also demonstrate favorable magnetic softness and considerable magnetic moment preserved at the interface and theoretically predict the interfacial band matching for spin filtering. Our work highlights the CoFeB/2D MoSe₂ interface as a promising platform for examination of TMD-based spintronic applications and might stimulate further development with other combinations of FM/2D TMD interfaces.