Effects of duodenal redox status on calcium absorption and related genes expression in high-fat diet-fed mice

Objective: This study investigated whether duodenal redox imbalance induced by high-fat diet (HFD) influenced expression of genes involved in transcellular calcium absorption, thus leading to reduced intestinal calcium absorption. Methods: Male C57BL/6 mice were randomly assigned to one of four groups with eight mice in each group. The control group consumed an ordinary diet (4.9% fat, w/w). The other three groups were fed a HFD (21.2% fat), the HFD plus 0.1% lipoic acid, or the HFD plus an additional 0.9% calcium supplement. After 9 wk, plasma and duodenal oxidative stress biomarkers including malondialdehyde, superoxide dismutase, catalase, total antioxidant capacity, reduced glutathione/oxidized glutathione ratio, and reactive oxygen species were examined. The intestinal calcium absorption state was evaluated through examining the calcium balance, bone mineral density, and calcium metabolism biomarkers. Furthermore, quantitative reverse transcription-polymerase chain reaction was carried out to analyze the changes in expression of transcellular calcium absorption-related genes. Results: The HFD induced marked decreases in intestinal calcium absorption and bone mineral density of the whole body, accompanied by redox imbalance and increased oxidative damage in duodenum; duodenal expression of calbindin-D-9K, plasma membrane calcium ATPase (PMCA(1b)). and sodium-calcium exchanger was significantly down-regulated by 1.9-, 2.7-, and 1.5-fold, respectively. Furthermore, duodenal glutathione and oxidized glutathione (GSH/GSSG) ratios were strongly positively correlated with the apparent calcium absorption rate and the expression of PMCA(1b) and Calbindin-D-9K, whereas reactive oxygen species levels were negatively correlated with them. Conclusion: Our results demonstrated that a HFD-induced duodenal oxidation state could significantly down-regulate expression of calbindin-D-9K, PMCA(1b), and sodium-calcium exchanger, thus causing an inhibitory effect on intestinal calcium absorption. (C) 2010 Elsevier Inc. All rights reserved.