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On September 7 and 8, 2022, Healthy Environment and Endocrine Disruptors Strategies, an Environmental Health Sciences program, convened a scientific workshop of relevant stakeholders involved in obesity, toxicology, or obesogen research to review the state of the science regarding the role of obesogenic chemicals that might be contributing to the obesity pandemic. The workshops objectives were to examine the evidence supporting the hypothesis that obesogens contribute to the etiology of human obesity; to discuss opportunities for improved understanding, acceptance, and dissemination of obesogens as contributors to the obesity pandemic; and to consider the need for future research and potential mitigation strategies. This report details the discussions, key areas of agreement, and future opportunities to prevent obesity. The attendees agreed that environmental obesogens are real, significant, and a contributor at some degree to weight gain at the individual level and to the global obesity and metabolic disease pandemic at a societal level; moreover, it is at least, in theory, remediable.

The endangered crocodile lizard, Shinisaurus crocodilurus, is seriously imperiled by anthropogenic threats, including habitat loss and degradation and most critically over-collection for the international pet trade. As a result, population sizes of crocodile lizards have sharply declined throughout their range, with only a small number remaining in China and a handful of individuals left in Vietnam. To prioritize conservation measures for the species, in this study, we generate new mitochondrial sequences of important new samples and analyze them with existing data. Our results confirm a new genetically distinct population in China, highlighting cryptic genetic diversity within the species. The assessment of climate change impacts on the species suggests that the suitable habitat of one population in China will become severely fragmented, decreased in size, and shifted, while the habitat of two other Chinese populations will remain stable and may even expand given future climate scenarios. In Vietnam, Yen Tu Mountain Range is predicted to serve as a refuge in different climate change projections, but suitable habitat in the border area between Vietnam and China will likely shift geographically. Based on our results, we recommend further field surveys to locate the natural distribution range of the newly identified molecular clade in China and determine the distribution extension of the Vietnamese population in the border area, especially potential occurrence on the Chinese side. Considering the impacts of climate change on the Vietnamese population, designing a corridor to connect the subpopulation’s habitat in the border area with nature reserves in Yen Tu Mountain Range and/or translocating lizards from the site to more suitable habitats might help secure the subpopulation in the context of climate change. In all recommended conservation measures, close collaboration between Vietnam and China will be crucial to effectively protect this potentially shared subpopulation of the highly threatened species.

Climate change has potential effects on global biodiversity by shifting the optimal distribution of terrestrial organisms, particularly species with narrow distributions. Goniurosaurus lichtenfelderi, a forest-dwelling lizard, is found on both the islands and mainland of northern Vietnam and southern China. The species is categorized as Vulnerable in the IUCN Red List and was recently listed in CITES Appendix II and the Vietnam Government’s Decree 06 in 2019 due to severe anthropogenic impacts on its populations. In this study, we employ Maxent species distribution modeling with climatic and vegetation cover data to identify the potential distribution of G. lichtenfelderi. We also used this approach to assess future climate impacts on the potential distribution under different climate change scenarios. Our model predicts that the potential distribution of G. lichtenfelderi will shrink significantly under future scenarios and even vanish in the entire study area under novel environmental conditions of the BCC-CSM 1-1 – RCP 8.5 scenario by the 2070s. Overall, the current potential distribution is expected to shift towards higher latitudes within the next decades. The forecasted maps provide useful guidelines to implement conservation strategies to mitigate synergistic impacts from climate change and other negative anthropogenic activities. In the context of the potentially severe impacts, the border areas between China and Vietnam, Yen Tu Mountain Range, Bai Tu Long National Park, and their surroundings should be considered core refugia for the species, where conservation measures need to be prioritized in the future.

The Microhyla heymonsi species complex from central Vietnam was examined, and based upon morphological and molecular evidence, two new species are described. The discovery of Microhyla daklakensis sp. nov. and Microhyla ninhthuanensis sp. nov. brings the total number of known species in the genus to 46 and the species number of Microhyla in Vietnam to 13. The Truong Son Range harbors the highest diversity of the genus Microhyla with 11 recorded species so far. However, this apparent micro-endemic diversity is at risk because of habitat loss by deforestation, which highlights the necessity of further research leading to improved conservation measures.

Climate change has potential effects on global biodiversity by shifting the optimal distribution of terrestrial organisms, particularly species with narrow distributions. Goniurosaurus lichtenfelderi, a forest-dwelling lizard, is found on both the islands and mainland of northern Vietnam and southern China. The species is categorized as Vulnerable in the IUCN Red List and was recently listed in CITES Appendix II and the Vietnam Government’s Decree 06 in 2019 due to severe anthropogenic impacts on its populations. In this study, we employ Maxent species distribution modeling with climatic and vegetation cover data to identify the potential distribution of G. lichtenfelderi. We also used this approach to assess future climate impacts on the potential distribution under different climate change scenarios. Our model predicts that the potential distribution of G. lichtenfelderi will shrink significantly under future scenarios and even vanish in the entire study area under novel environmental conditions of the BCC-CSM 1-1 – RCP 8.5 scenario by the 2070s. Overall, the current potential distribution is expected to shift towards higher latitudes within the next decades. The forecasted maps provide useful guidelines to implement conservation strategies to mitigate synergistic impacts from climate change and other negative anthropogenic activities. In the context of the potentially severe impacts, the border areas between China and Vietnam, Yen Tu Mountain Range, Bai Tu Long National Park, and their surroundings should be considered core refugia for the species, where conservation measures need to be prioritized in the future.

BackgroundAdvances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues.AimWe performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome.MethodsWe studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p'-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways.ResultsConcentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for > 80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism.ConclusionsMost of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations.

There is limited understanding of the role of host metabolism in the pathophysiology of human tuberculosis (TB). Using high-resolution metabolomics with an unbiased approach to metabolic pathway analysis, we discovered that the tryptophan pathway is highly regulated throughout the spectrum of TB infection and disease. This regulation is characterized by increased catabolism of tryptophan to kynurenine, which was evident not only in active TB disease but also in latent TB infection (LTBI). Further, we found that tryptophan catabolism is reversed with effective treatment of both active TB disease and LTBI in a manner commensurate with bacterial clearance. Persons with active TB and LTBI also exhibited increased expression of indoleamine 2,3-dioxygenase-1 (IDO-1), suggesting IDO-1 mediates observed increases in tryptophan catabolism. Together, these data indicate IDO-1-mediated tryptophan catabolism is highly preserved in the human response to Mycobacterium tuberculosis and could be a target for biomarker development as well as host-directed therapies.

Background Correction of nutritional vitamin deficiency is recommended in children with chronic kidney disease (CKD). The optimal daily dose of vitamin D to achieve or maintain vitamin D sufficiency is unknown. Methods We conducted a phase III, double-blind, randomized trial of two doses of vitamin D.sub.3 in children [greater than or equal to] 9 years of age with CKD stages 3-5 or kidney transplant recipients. Patients were randomized to 1000 IU or 4000 IU of daily vitamin D.sub.3 orally. We measured 25-hydroxvitamin D (25(OH)D) levels at baseline, 3 months and 6 months. The primary efficacy outcome was the percentage of patients who were vitamin D replete (25(OH)D [greater than or equal to] 30 ng/mL) at 6 months. Results Ninety-eight patients were enrolled: 49 randomized into each group. Eighty (81.6%) patients completed the study and were analyzed. Baseline plasma 25(OH)D levels were [greater than or equal to] 30 ng/mL in 12 (35.3%) and 12 (27.3%) patients in the 1000 IU and 4000 IU treatment groups, respectively. At 6 months, plasma 25(OH)D levels were [greater than or equal to] 30 ng/mL in 33.3% (95% CI: 18.0-51.8%) and 74.4% (95% CI: 58.8-86.5%) in the 1000 IU and 4000 IU treatment groups, respectively (p = 0.0008). None of the patients developed vitamin D toxicity or hypercalcemia. Conclusions In children with CKD, 1000 IU of daily vitamin D.sub.3 is unlikely to achieve or maintain a plasma 25(OH)D [greater than or equal to] 30 ng/mL. In children with CKD stages 3-5, a dose of vitamin D.sub.3 4000 IU daily was effective in achieving or maintaining vitamin D sufficiency. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT01909115 Graphical abstract, Author(s): Shahid Nadeem [sup.1] , Vin Tangpricha [sup.2] , Thomas R. Ziegler [sup.3] , James E. Rhodes [sup.4] , Traci Leong [sup.5] , Yijin Xiang [sup.6] , Larry A. Greenbaum [...]

Chronic kidney disease (CKD) leads to decreased sensitivity to the metabolic effects of insulin, contributing to protein energy wasting and muscle atrophy. Targeted metabolomics profiling during hyperinsulinemic-euglycemic insulin clamp testing may help identify aberrant metabolic pathways contributing to insulin resistance in CKD. Using targeted metabolomics profiling, we examined the plasma metabolome in 95 adults without diabetes in the fasted state (58 with CKD, 37 with normal glomerular filtration rate [GFR]) who underwent hyperinsulinemic-euglycemic clamp. We assessed heterogeneity in fasting metabolites and the response to insulin to identify potential metabolic pathways linking CKD with insulin resistance. Baseline differences and effect modification by CKD status on changes with insulin clamp testing were adjusted for confounders. Mean GFR among participants with CKD was 37.3 compared with 89.3 ml/min per 1.73 m2 among controls. Fasted-state differences between CKD and controls included abnormalities in tryptophan metabolism, ubiquinone biosynthesis, and the TCA cycle. Insulin infusion markedly decreased metabolite levels, predominantly amino acids and their metabolites. CKD was associated with attenuated insulin-induced changes in nicotinamide, arachidonic acid, and glutamine/glutamate metabolic pathways. Metabolomics profiling suggests disruption in amino acid metabolism and mitochondrial function as putative manifestations or mechanisms of the impaired anabolic effects of insulin in CKD.