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Background: Non-caloric artificial sweeteners (NCAS) are widely used as a substitute for dietary sugars to control body weight or glycemia. Paradoxically, some interventional studies in humans and rodents have shown unfavorable changes in glucose homeostasis in response to NCAS consumption. The causative mechanisms are largely unknown, but adverse changes in gut microbiota have been proposed to mediate these effects. These findings have raised concerns about NCAS safety and called into question their broad use, but further physiological and dietary considerations must be first addressed before these results are generalized. We also reasoned that, since NCAS are bona fide ligands for sweet taste receptors (STRs) expressed in the intestine, some metabolic effects associated with NCAS use could be attributed to a common mechanism involving the host., Results: We conducted a double-blind, placebo-controlled, parallel arm study exploring the effects of pure saccharin compound on gut microbiota and glucose tolerance in healthy men and women. Participants were randomized to placebo, saccharin, lactisole (STR inhibitor), or saccharin with lactisole administered in capsules twice daily to achieve the maximum acceptable daily intake for 2 weeks. In parallel, we performed a 10-week study administering pure saccharin at a high dose in the drinking water of chow-fed mice with genetic ablation of STRs (T1R2-KO) and wild-type (WT) littermate controls. In humans and mice, none of the interventions affected glucose or hormonal responses to an oral glucose tolerance test (OGTT) or glucose absorption in mice. Similarly, pure saccharin supplementation did not alter microbial diversity or composition at any taxonomic level in humans and mice alike. No treatment effects were also noted in readouts of microbial activity such as fecal metabolites or short-chain fatty acids (SCFA). However, compared to WT, T1R2-KO mice were protected from age-dependent increases in fecal SCFA and the development of glucose intolerance., Conclusions: Short-term saccharin consumption at maximum acceptable levels is not sufficient to alter gut microbiota or induce glucose intolerance in apparently healthy humans and mice., Trial Registration: Trial registration number NCT03032640 , registered on January 26, 2017. Video abstract.

Background: Mining, agriculture and cattle production are activities that threaten the quality and quantity of water resources in the Colombian Andes. However, many drainage basins in this region have not been subjected to simultaneous evaluation of the impact these activities have on the density, diversity and composition of aquatic macroinvertebrates (AMI). The first two of these ecological variables are expected to decrease drastically from zones with no apparent impact towards areas with anthropogenic activity, which areas with mining will present the most impoverished AMI community., Methods: We evaluated the density, diversity and composition dissimilarity of AMI in streams impacted by gold mining, agriculture and cattle production. Two reference streams were also studied. Six benthic samplings were conducted bimonthly (Feb 2014-Feb 2015) using a Surber net. Water samples were taken in order to make environmental evaluation among the aforementioned streams, including hydrological, physicochemical and bacteriological parameters (HPCB). Diversity was evaluated as the effective number of RTUs-recognizable taxonomic units-by comparing the richness, typical diversity, and effective number of the most abundant RTUs. Compositional dissimilarity was examined with nMDS and CCA analysis., Results: A total of 7,483 organisms were collected: 14 orders, 42 families and 71 RTUs. Our prediction regarding the density and diversity of AMI (Reference > Cattle production > Agriculture > Mining) was partially fulfilled, since the agriculture-dominated stream presented a more impoverished AMI community than that of the gold mining stream. However, these streams presented lower diversity than the cattle production and reference streams, and the AMI density only differed significantly between one reference stream and the agriculture stream. The AMI composition in the agriculture-dominated stream clearly differed from that of the other streams., Discussion: The observation of a more impoverished AMI community in agricultural production areas compared to those with mining or cattle production may reflect the importance of the remaining riparian vegetation, which was scarce at the stream with agricultural activity. Moreover, the low diversity, and mainly the reduced AMI richness, in the agriculture stream coincided with the absence of insect genera are intolerant to deterioration of the biological and physicochemical conditions of the water (e.g. Anacroneuria )., Conclusions: The results suggest that the local impact of agricultural activities may be of equal or greater magnitude than that of mining in terms of AMI density, diversity and composition, in the Colombian Andean riverscape. Future studies should systematically evaluate, throughout the annual cycle, the relative effects of the productive land use, the remaining native vegetation cover and the consequent changes in the HPCB parameters of the water on AMI communities in Colombian Andean basins., Competing Interests: The authors declare there are no competing interests., (©2020 Meza-Salazar et al.)

Differences in glucose uptake in peripheral and neural tissues account for the reduced efficacy of insulin in nervous tissues. Herein, we report the design of short peptides, referred as amino acid compounds (AAC) with and without a modified side chain moiety. At nanomolar concentrations, a candidate therapeutic molecule, AAC2, containing a 7-(diethylamino) coumarin-3-carboxamide side-chain improved glucose control in human peripheral adipocytes and the endothelial brain barrier cells by activation of insulin-insensitive glucose transporter 1 (GLUT1). AAC2 interacted specifically with the leptin receptor (LepR) and activated atypical protein kinase C zeta (PKCς) to increase glucose uptake. The effects induced by AAC2 were absent in leptin receptor-deficient predipocytes and in Lepr db mice. In contrast, AAC2 established glycemic control altering food intake in leptin-deficient Lep ob mice. Therefore, AAC2 activated the LepR and acted in a cytokine-like manner distinct from leptin. In a monogenic Ins2 Akita mouse model for the phenotypes associated with type 1 diabetes, AAC2 rescued systemic glucose uptake in these mice without an increase in insulin levels and adiposity, as seen in insulin-treated Ins2 Akita mice. In contrast to insulin, AAC2 treatment increased brain mass and reduced anxiety-related behavior in Ins2 Akita mice. Our data suggests that the unique mechanism of action for AAC2, activating LepR/PKCς/GLUT1 axis, offers an effective strategy to broaden glycemic control for the prevention of diabetic complications of the nervous system and, possibly, other insulin insensitive or resistant tissues., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Constantly, aquatic ecosystems are under pressure by complex mixtures of contaminants whose effects are not always easy to evaluate. Due to this, organisms are sought in which early warning signs may be detected upon the presence of potentially toxic xenobiotic substances. Thereby, the study evaluated the incidence of deformities and other morphometric variations in the mentum and wing of Chironomus columbiensis exposed to water from some of the Colombian Andes affected by mining, agriculture, and cattle raising. Populations of C. columbiensis were subjected throughout their life cycle (24 days) for two generations (F1 and F2). Five treatments were carried out in controlled laboratory conditions (water from the site without impact, site of mining mercury, mining mercury + cyanide, cattle raising, and agriculture) and the respective control (reconstituted water). Thereafter, the percentage of deformities in the mentum was calculated, and for the morphometric analysis 29 landmarks were digitized for the mentum and 12 for the wing. As a result, four types of deformities were registered in the C. columbiensis mentum, like absence of teeth, increased number of teeth, fusion and space between teeth, none of them detected in the individuals from the control. Additionally, the highest incidence of deformity in F1 occurred in the treatment of mining mercury, while for F2 this took place in the treatments of mining mercury + cyanide, cattle raising and agriculture. Differences were also found with respect to the morphometric variations of the mentum and wing of C. columbiensis among the control and the treatments with water from the creeks intervened. The treatments of mining mercury + cyanide and agriculture had the highest morphological variation in the mentum and wing of C. columbiensis. The results suggest that the anthropogenic impacts evaluated generate alterations in the oral apparatus of the larval state of C. columbiensis and in the adult state provoke alterations in the wing shape (increased width and reduced basal area). These deformities may be related to multiple stress factors, among them the xenobiotics metabolized by the organisms under conditions of environmental contamination., Competing Interests: The authors have declared that no competing interests exist.