White adipose tissue (WAT) is a dynamic organ that plays crucial roles in controlling metabolic homeostasis. During development and periods of energy excess, adipose progenitors are recruited and differentiate into adipocytes to promote lipid storage capability. The identity of adipose progenitors and the signals that promote their recruitment are still incompletely characterized. We have recently identified V-set and transmembrane domain-containing protein 2A (VSTM2A) as a novel protein enriched in preadipocytes that amplifies adipogenic commitment. Despite the emerging role of VSTM2A in promoting adipogenesis, the molecular mechanisms regulating Vstm2a expression in preadipocytes are still unknown. To define the molecular mechanisms controlling Vstm2a expression, we have treated preadipocytes with an array of compounds capable of modulating established regulators of adipogenesis. Here, we report that Vstm2a expression is positively regulated by PI3K/mTOR and cAMP-dependent signaling pathways and repressed by the MAPK pathway and the glucocorticoid receptor. By integrating the impact of all the molecules tested, we identified signal transduced and activator of transcription 3 (STAT3) as a novel downstream transcription factor affecting Vstm2a expression. We show that activation of STAT3 increased Vstm2a expression, whereas its inhibition repressed this process. In mice, we found that STAT3 phosphorylation is elevated in the early phases of WAT development, an effect that strongly associates with Vstm2a expression. Our findings identify STAT3 as a key transcription factor regulating Vstm2a expression in preadipocytes.
Vaping is increasingly popular among the young and adult population. Vaping liquids contained in electronic cigarettes (e‐cigarettes) are mainly composed of propylene glycol and glycerol, to which nicotine and flavors are added. Among several biological processes, glycerol is a metabolic substrate used for lipid synthesis in fed state as well as glucose synthesis in fasting state. We aimed to investigate the effects of glycerol e‐cigarette aerosol exposure on the aspects of glycerol and glucose homeostasis. Adult and young male and female mice were exposed to e‐cigarette aerosols with glycerol as vaping liquid using an established whole‐body exposure system. Mice were exposed acutely (single 2‐h exposure) or chronically (2 h/day, 5 days/week for 9 weeks). Circulating glycerol and glucose levels were assessed and glycerol as well as glucose tolerance tests were performed. The liver was also investigated to assess changes in the histology, lipid content, inflammation, and stress markers. Lung functions were also assessed as well as hepatic mRNA expression of genes controlling the circadian rhythm. Acute exposure to glycerol aerosols generated by an e‐cigarette increased circulating glycerol levels in female mice. Increased hepatic triglyceride and phosphatidylcholine concentrations were observed in female mice with no increase in circulating alanine aminotransferase or evidence of inflammation, fibrosis, or endoplasmic reticulum stress. Chronic exposure to glycerol e‐cigarette aerosols mildly impacted glucose tolerance test in young female and male mice. Fasting glycerol, glucose, and insulin remained unchanged. Increased pulmonary resistance was observed in young male mice. Taken together, this study shows that the glycerol contained in vaping liquids can affect the liver as well as the aspects of glucose and glycerol homeostasis. Additional work is required to translate these observations to humans and determine the biological and potential pathological impacts of these findings.
Objectives: To identify patient-related factors and fracture characteristics influencing the functional outcomes of non-operatively treated radial head fractures and to determine function at one year. Design: Prospective cohort study Setting: Academic level 1 trauma center Patients/Participants: Consecutive isolated radial head fractures fitting the inclusion criteria between May 2013 and July 2016. Intervention: Nonoperative treatment of isolated radial head fractures. Outcome measurements: Logistic regressions between potential prognostic factors and function assessed with the Mayo Elbow Performance Score (MEPS), the Disabilities of the Arm, Shoulder and Hand (DASH) score and Range of Motion (ROM) at 1.5-3-6-12 months. Results: 114 patients were included (78% Mason I [OTA/AO 2R1B1], 20% Mason II [OTA/AO 2R1B3] and 2% Mason III [OTA/AO 2R1C3]). Mean MEPS and DASH score at the last follow-up were excellent [96.4 ± 7.6 and 3.7 ± 8.6] with respectively 79.8% and 92.7% of satisfactory results. Depressive symptoms at injury baseline (Quick Inventory of Depressive Symptomatology > 5) are a constant predictor of unsatisfactory function (MEPS <90 or DASH >17]). Older age and female sex were all linked to worse function at the first follow-ups (p <0.05), whereas lower socioeconomic class and receiving financial compensations were associated to unsatisfactory function at 1-year (p <0.05). Conclusions: While most non-operatively treated radial head fractures heal with excellent function, some patients still exhibit unsatisfactory results at 1-year. Symptoms of depression at injury baseline are a constant and significant predictor of unsatisfactory function. Early detection of depressive symptoms would allow interventions that may optimize function.
Rationale: Vaping products contain numerous flavor compounds that are known immunological sensitizers. Sensitization to various antigens can be responsible for the onset of serious respiratory diseases, including hypersensivity pneumonitis. However, respiratory tract sensitization and pathological consequences from exposure to aerosols of flavored vaping liquids need to be thoroughly investigated. Methods: Female BALB/c mice were exposed to laboratory made nicotine-free vaping liquid containing a mixture of 1% citral (lemon), 1% cinnamaldehyde (cinnamon), 1% dihydrocoumarin (coconut) and 1% vanillin (vanilla) solubilized in propylene glycol and glycerol (50:50). Mice were exposed 2h/day for 4 days to vaping or room air. Bronchoalveolar lavage was performed to assess total and differential cell counts, and flow cytometry was performed on pulmonary tissue and lung-draining lymph nodes to assess immune cell populations. Results: After 4 days of daily exposure, we found a significant increase in bronchoalveolar lavage immune cells in mice exposed to aerosols from the flavored vaping liquid. We also observed a significant increase in pulmonary conventional dendritic cells (cDCs) as well as their expression of the activation markers CD40, CD86 and MHC-II. This activation is mainly observed on type 2 cDCs. In the lung-draining lymph nodes, flavored vaping liquid lead to a significant increase in total immune cells (CD45+ cells). Conclusions: Pulmonary conventional dendritic cells activation and the increase in total immune cells in lung-draining lymph nodes caused by exposure to aerosols from flavored vaping liquid suggest the early initiation of immunological sensitization processes in the lungs. Fonds de recherche du Québec – Santé, Ministère de la Santé et des Services sociaux, Fondation de l’Institut de cardiologie et de pneumologie de Québec, Réseau de recherche en santé respiratoire du Québec.
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