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Background/Objectives: As a hyperaccumulator of selenium (Se), Cardamine violifolia (Cv) and its peptide extract could ameliorate the negative effects of a high-fat diet (HFD). However, the effects of the coaccumulation of cadmium (Cd) in Se-enriched Cv (Cv2) and the potential confounding effect on the roles of enriched Se remain unknown. We aimed to investigate whether Cv2 could alleviate HFD-induced lipid disorder and liver damage. Methods: Three groups of 31-week-old female mice were fed for 41 weeks (n = 10–12) with a control Cv-supplemented diet (Cv1D, 0.15 mg Se/kg, 30 µg Cd/kg, and 10% fat calories), a control Cv-supplemented HFD (Cv1HFD, 45% fat calories), and a Cv2-supplemented HFD (Cv2HFD, 1.5 mg Se/kg, 0.29 mg Cd/kg, and 45% fat calories). Liver and serum were collected to determine the element concentrations, markers of liver injury and lipid disorder, and mRNA and/or protein expression of lipid metabolism factors, heavy metal detoxification factors, and selenoproteins. Results: Both Cv1HFD and Cv2HFD induced obesity, and Cv2HFD downregulated Selenoi and upregulated Dio3 compared with Cv1D. When comparing Cv2HFD against Cv1HFD, Cv2 increased the liver Se and Cd, the protein abundance of Selenoh, and the mRNA abundance of 10 selenoproteins; reduced the serum TG, TC, and AST; reduced the liver TG, lipid droplets, malondialdehyde, and mRNA abundance of Mtf1 and Mt2; and differentially regulated the mRNA levels of lipid metabolism factors. Conclusions: Cv2 alleviated HFD-induced lipid dysregulation and liver damage, which was probably associated with its unique Se speciation. However, further research is needed to explore the interaction of plant-coenriched Se and Cd and its effects on health. [ABSTRACT FROM AUTHOR]

Our laboratory previously revealed that regenerating islets-derived protein 2 (REG2) was diminished in pancreatic islets of glutathione peroxidase-1-overexpressing mice (Gpx1-OE). It remained unknown if there is an inverse relationship between the expression and function of all Reg family genes and antioxidant enzymes in the pancreatic islets or human pancreatic cells. This research was to determine how altering the Gpx1 and superoxide dismutase-1 (Sod1) genes alone or together (dKO) affected the expression of all seven murine Reg genes in murine pancreatic islets. In Experiment 1, Gpx1-/-, Gpx1-OE, their wild-type (WT), Sod1-/-, dKO, and their WT (male, 8-wk old, n = 4–6) were fed a Se-adequate diet and their islets were collected to assay the mRNA levels of Reg family genes. In Experiment 2, islets from the six groups of mice were treated with phosphate-buffered saline (PBS), REG2, or REG2 mutant protein (1 µg/mL), and/or GPX mimic (ebselen, 50 µM) and SOD mimic (copper [II] diisopropyl salicylate, CuDIPS, 10 µM) for 48 h before the proliferation assay using bromodeoxyuridine (BrdU). In Experiment 3, human pancreatic cells (PANC1) were treated with REG2 (1 µg/mL) and assayed for REG gene expression, GPX1 and SOD1 activities, viability, and responses to Ca2+. Compared with the WT, knockouts of Gpx1 and/or Sod1 up-regulated (p < 0.05) the mRNA levels of most of the murine Reg genes in islets whereas the Gpx1 overexpression down-regulated (p < 0.05) Reg mRNA levels. REG2, but not the REG2 mutant, inhibited islet proliferation in Gpx1 or Sod1-altered mice. Such inhibition was abolished by co-incubation the Gpx1-/- islets with ebselen and the Sod1-/- islets with CuDIPS. Treating PANC1 cells with murine REG2 protein induced expression of its human orthologue REG1B and three other REG genes, but decreased SOD1 and GPX1 activities and cell viability. In conclusion, our results revealed an interdependence of REG family gene expression and/or function on intracellular GPX1 and SOD1 activities in murine islets and human pancreatic cells. [ABSTRACT FROM AUTHOR]

Transition metals such as iron, copper and zinc are required for the normal functioning of biological tissues, whereas others, such as cadmium, are potentially highly toxic. Any disturbances in homeostasis caused by lack of micronutrients in the diet, pollution or genetic heredity result in malfunction and/or diseases. Here, we used synchrotron X-ray fluorescence, SXRF, microscopy and mice with altered functions of major antioxidant enzymes to show that SXRF may become a powerful tool to study biologically relevant metal balance in the pancreas and liver of mice models with disturbed glucose homeostasis. [ABSTRACT FROM AUTHOR]