16Objectives: To investigate the early cardiometabolic abnormalities along with WAT and BAT 17 remodeling in short-term fructose feeding mice model. Methods: Mice (n=10-11/group) were fed 18 for four weeks with control diet (AIN93-M) or experimental diets rich in glucose or fructose. We 19 investigated body weight, body adiposity, blood glucose, lipid and hepatic parameters, and white 20 (WAT) and brown adipose tissue (BAT) histopathology. Results: Fructose feeding promoted 21 neither weight gain nor hypertrophy of visceral and subcutaneous WAT depots, but the fat was 22 redistributed toward visceral depots. Glucose, lipid and hepatic metabolic dysfunction were not yet 23 noticed in fructose-fed mice, with the exception for an elevation in total cholesterol and hepatic 24 weight without steatosis. BAT mass did not increase, and it was proportionally reduced compared 25 with visceral WAT in fructose feed mice. BAT suffered premature adverse morphological 26 remodeling, characterized by increased lipid deposition per tissue area in enlarged intracellular lipid 27 droplets. Conclusion: Short-term fructose feeding redistributes body fat, changes the proportion of 28 BAT to visceral fat, and promotes BAT adverse remodeling, characterized by enlarged intracellular 29 lipid droplets. 30
Invasive pulmonary aspergillosis is a life-threatening fungal infection especially in the immunocompromised patients. The low diversity of available antifungal drugs coupled with the emergence of antifungal resistance has become a worldwide clinical concern. The echinocandin Caspofungin (CSP) is recommended as a second-line therapy but resistance and tolerance mechanisms have been reported. However, how the fungal cell articulates the response to CSP is not completely understood. This work provides a detailed characterization of ZnfA, a transcription factor (TF) identified in previous screening studies that is involved in the A. fumigatus responses to calcium and CSP. This TF plays an important role in the regulation of iron homeostasis and cell wall organization in response to high CSP concentrations as revealed by Chromatin Immunoprecipitation coupled to DNA sequencing (ChIP-seq) analysis. Furthermore, ZnfA acts collaboratively with the key TF CrzA in modulating the response to calcium as well as cell wall and osmotic stresses. This study therefore describes the existence of an additional, previously unknown TF that bridges calcium signaling and the CSP cellular response and further exposes the complex connections that exist among different pathways which govern stress sensing and signaling in A. fumigatus.
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