Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring

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Abstract

Maternal dietary modifications determine the susceptibility to metabolic diseases in adult life. However, whether maternal high-fat feeding can modulate glucose and lipid metabolism in the early life of offspring is less understood. Furthermore, we explored the underlying mechanisms that influence the phenotype. Using C57BL/6J mice, we examined the effects on the offspring at weaning from dams fed with a high-fat diet or normal chow diet throughout pregnancy and lactation. Gene array experiments and quantitative real-time PCR were performed in the liver tissues of the offspring mice. The offspring of the dams fed the high-fat diet had a heavier body weight, impaired glucose tolerance, decreased insulin sensitivity, increased serum cholesterol and hepatic steatosis at weaning. Bioinformatic analyses indicated that all differentially expressed genes of the offspring between the two groups were mapped to nine pathways. Genes in the peroxisome proliferator-activated receptor (PPAR) signaling pathway were verified by quantitative real-time PCR and these genes were significantly up-regulated in the high-fat diet offspring. A maternal high-fat diet during pregnancy and lactation can modulate hepatic glucose, lipid homeostasis, and gene expression in the PPAR signaling in the early life of offspring, and our results suggested that potential mechanisms that influences this phenotype may be related partially to up-regulate some gene expression in the PPAR signalling pathway. © 2014 by the authors; licensee MDPI, Basel, Switzerland.

Figures

  • Figure 1. Birth weight and body weight at weaning in the offspring from the high-fat diet and normal chow diet groups. (A) Birth weight; and (B) body weight. Data represented as the mean ± standard deviation (S.D.) (n = 16, per group, 8 male and 8 female). * p < 0.05 vs. the normal chow diet group. HFD, high-fat diet; NCD, normal chow diet.
  • Figure 2. Glucose metabolism parameters of the offspring at weaning in the high-fat diet and normal chow diet groups. (A) IPGTT; (B) AUC; (C) Serum insulin levels; (D) HOMA-IR. Data represented as the mean ± S.D. (n =16, per group, 8 male and 8 female). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the normal chow diet group. HFD, high-fat diet; NCD, normal chow diet; IPGTT, intraperitoneal glucose tolerance test; AUC, area under the curve; HOMA-IR, the homeostasis model assessment of insulin resistance.
  • Figure 3. Lipid metabolism parameters of the offspring at weaning in the high-fat diet and normal chow diet groups. (A) Serum triacyglycerol and (B) total cholesterol; (C) Liver histology of haematoxylin and eosin staining in the offspring from the dams fed a normal chow diet had normal liver structure; (D) Lipid vacuoles (red arrow) of various sizes were observed within the hepatocytes of the offspring from the dams fed a high-fat diet. Original magnification, 40×. Data represented as the mean ± S.D. (n =16, per group, 8 male and 8 female). *** p < 0.001 vs. the normal chow diet group. HFD, high-fat diet; NCD, normal chow diet.
  • Table 1. The comparison of biochemical parameters of the male and female offspring at weaning in the high-fat diet and normal chow diet groups. Data represented as the mean ± S.D. (n = 8 per group of male and female). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the normal chow diet group.
  • Figure 4. Gene array data analysis of the offspring between the high-fat diet and normal chow diet groups. (A) Heatmap diagram: this diagram illustrates the differential expression of hepatic mRNAs in the high-fat diet (n = 3) compared with the normal chow diet offspring (n = 3). The tree was based on the log2 transformation of the normalised probe signal intensity using hierarchical clustering. The hierarchical clustering was based on 380 differentially expressed mRNAs; the expression levels were differentially expressed in the high-fat diet group, with red representing increased expression and green representing decreased expression; (B) The Volcano Plot graphs: this graph shows the log2 of the fold change in each gene’s expression between the two group and its p value from the t-test. The blue lines indicate that the fold change in the gene expression threshold is 2. The pink line indicates that the p value of the t-test threshold is 0.05. There were four genes, which showed significantly different expression between the two groups, in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Aqp7, aquaporin 7; Cpt1b, carnitine palmitoyltransferase 1b; Fabp2, fatty acid binding protein 2; HFD, high-fat diet; NCD, normal chow diet.
  • Table 2. Gene ontology (GO) groups with differentially expressed genes in the high-fat diet offspring (p < 0.05).
  • Table 3. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways with differentially expressed genes in the high-fat diet offspring (fold change > 2.0, p < 0.05).
  • Table 4. Fold change of gene expression measured by gene array and qRT-PCR. Aqp7, aquaporin 7; Cpt1b, carnitine palmitoyltransferase 1b; Fabp2, fatty acid binding protein 2.

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APA

Zheng, J., Xiao, X., Zhang, Q., Yu, M., Xu, J., & Wang, Z. (2014). Maternal high-fat diet modulates hepatic glucose, lipid homeostasis and gene expression in the PPAR pathway in the early life of offspring. International Journal of Molecular Sciences, 15(9), 14967–14983. https://doi.org/10.3390/ijms150914967

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