The effect of maternal chromium status on lipid metabolism in female elderly mice offspring and involved molecular mechanism

Qian Zhang, Xiaofang Sun, Xinhua Xiao, Jia Zheng, Ming Li, Miao Yu, Fan Ping, Zhixin Wang, Cuijuan Qi, Tong Wang, Xiaojing Wang, Qian Zhang, Xiaofang Sun, Xinhua Xiao, Jia Zheng, Ming Li, Miao Yu, Fan Ping, Zhixin Wang, Cuijuan Qi, Tong Wang, Xiaojing Wang

Abstract

Maternal malnutrition leads to the incidence of metabolic diseases in offspring. The purpose of this project was to examine whether maternal low chromium could disturb normal lipid metabolism in offspring, altering adipose cell differentiation and leading to the incidence of lipid metabolism diseases, including metabolic syndrome and obesity. Female C57BL mice were given a control diet (CD) or a low chromium diet (LCD) during the gestational and lactation periods. After weaning, offspring was fed with CD or LCD. The female offspring were assessed at 32 weeks of age. Fresh adipose samples from CD-CD group and LCD-CD group were collected. Genome mRNA were analysed using Affymetrix GeneChip Mouse Gene 2.0 ST Whole Transcript-based array. Differentially expressed genes (DEGs) were analysed based on gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis database. Maternal low chromium irreversibly increased offspring body weight, fat-pad weight, serum triglyceride (TG) and TNF-α. Eighty five genes increased and 109 genes reduced in the offspring adipose of the maternal low chromium group. According to KEGG pathway and String analyses, the PPAR signalling pathway may be the key controlled pathway related to the effect of maternal low chromium on female offspring. Maternal chromium status have long-term effects of lipid metabolism in female mice offspring. Normalizing offspring diet can not reverse these effects. The potential underlying mechanisms are the disturbance of the PPAR signalling pathway in adipose tissue.

Keywords: PPAR pathway; chromium; development; gene expression; lipid metabolism.

Conflict of interest statement

The authors declare that there are no competing inerests associated with the manuscript.

© 2017 The Author(s).

Figures

Figure 1. Timeline of animal experiment
Figure 1. Timeline of animal experiment
Time schedule of the animal experiment. Female mice received the CD or LCD during the gestational and lactation periods. The female offspring were monitored at birth, 3 weeks and 8 months of age.
Figure 2. Metabolic indicators affected by maternal…
Figure 2. Metabolic indicators affected by maternal low chromium diet
Serum chromium level (a) at 8 months of age in offspring, birth weight (b), weaning weight (c), and body weight (d), food intake (e), fat pad weight (f), serum TG (g), TC (h), HDL-C (i), LDL-C (j), leptin (k), adiponectin (l), TNF-α (m), IL-6 (n) and IL-1β (o) at 8 months of age in offspring. Values are mean ± S.D. (n=8); *P<0.05, ** P<0.01.
Figure 3. Hierarchical clustering of differently expressed…
Figure 3. Hierarchical clustering of differently expressed genes between LCD-CD group and CD-CD group
Hierarchical clustering of the 1.5-fold up-regulated and down-regulated genes. ‘Red’ indicates high relative expression; ‘green’ low relative expression. Samples F1, F3, F7 belong to LCD–CD group; samples F85, F86 and F88 belong to CD–CD group.
Figure 4. Volcano Plot of all genes…
Figure 4. Volcano Plot of all genes in gene array (LCD-CD group vs CD-CD group)
Volcano plot of genes in gene array. The red lines represent 1.5-fold up- and down-regulation and the blue line shows a P-value of 0.05. The dots in right block above the blue line are up-regulated genes; the dots in left block above the blue line are down-regulated genes.
Figure 5. GO biological process classification affected…
Figure 5. GO biological process classification affected by maternal low chromium diet
The most obvious changes in GO biological process classification.
Figure 6. PPAR sinaling pathway affected by…
Figure 6. PPAR sinaling pathway affected by maternal low chromium diet
All the different expression genes in PPAR pathway. Red represents up-regulated; green represents down-regulated; grey represents no significant change.
Figure 7. Gene interaction networks affected by…
Figure 7. Gene interaction networks affected by maternal low chromium diet
Interaction networks maps of DEGs. Thirteen nodes (more than 10 joint edges for each node) have total 190 joint edges, represents 88% of all the DEGs.
Figure 8. Real time PCR validation of…
Figure 8. Real time PCR validation of differently expressed genes
Real time PCR result of DEGs.
Figure 9. Schematic illustration of the effect…
Figure 9. Schematic illustration of the effect of maternal low chromium on offspring through PPARγ pathway.
PPARγ serves a key part in the regulation of adipocyte differentiation, adipogenesis and lipid metabolism, which are affected by maternal LCD in offspring adipose tissue. Maternal LCD triggers offspring adipose PPARγ pathway through activating ZFP423, CCAAT/enhancer-binding protein α (CEBPα) and SREBP1. Activated PPARγ binds to retinoid X receptor (RXR), enhancing its downstream target adipogenesis enzymes (Fabp3 and Lpl) and conversely inducing SREBP1 and CEBPα to increase circulation TGs.

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