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.


CONCLUSIONS
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.
Xiao
Ying
Y
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China.
Cui
Jue
J
Shi
Yong-Hui
YH
Sun
Jin
J
Wang
Zhou-Ping
ZP
Le
Guo-Wei
GW
D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D015519:Bone Density; D064026:Calbindins; D002118:Calcium / Q000008:administration & dosage / Q000378:metabolism*; D002136:Calcium, Dietary / Q000627:therapeutic use; D004041:Dietary Fats / Q000009:adverse effects*; D019587:Dietary Supplements; D004386:Duodenum / Q000201:enzymology / Q000502:physiology*; D005786:Gene Expression Regulation; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000097:blood / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000097:blood / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D008063:Thioctic Acid / Q000627:therapeutic use
D000975:Antioxidants; D015415:Biomarkers; D064026:Calbindins; D002136:Calcium, Dietary; D004041:Dietary Fats; C499849:NCX1 protein, mouse; C556012:Pmca1b protein, mouse; D017382:Reactive Oxygen Species; D064030:S100 Calcium Binding Protein G; D019831:Sodium-Calcium Exchanger; D008063:Thioctic Acid; D010088:Oxidoreductases; D053499:Plasma Membrane Calcium-Transporting ATPases; D005978:Glutathione; D002118:Calcium