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Shifting to a control diet after a high-fat, high-sucrose diet intake induces epigenetic changes in retroperitoneal adipocytes of Wistar rats

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Abstract

The aim of the study was to analyze the phenotypic and epigenetic changes induced by the shift to a chow diet after an obesogenic environment. Animals were randomized to fed chow (control group) or high-fat–sucrose diet (HFS). After 10 weeks, half of the rats fed with HFS diet were reassigned to a chow diet (rest group) while the other half continued with the obesogenic diet (HFS group) until week 20. Changes in fat content, biochemical profile, and DNA methylation levels of several gene promoters from retroperitoneal adipocytes were analyzed. HFS diet intake for 10 weeks induced obese phenotype in the animals, increasing body weight and fat content. These effects were maintained until the end of the trial in HFS group, where an increase in liver fat content, a modification of lipid profile, and retroperitoneal adipose tissue hypertrophy were also observed. Changing the dietary pattern reversed these parameters. Epigenetic analysis showed that HFS diet intake for 20 weeks hypermethylated several CpG sites (6.7 and 29.30) and hypomethylated CpG site 15 from leptin gene promoter. Moreover, the obesogenic diet also hypomethylated CpG site 1 from Fasn (fatty acid synthase) gene promoter, without changes on Ppargc1a (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), Srebf1 (sterol regulatory element-binding transcription factor 1), and aquaporin 7. Shifting to a chow diet reverted HFS-induced DNA methylation levels of some CpG sites of leptin promoter. Changing the dietary pattern hypomethylated a CpG site of Srebf1 and hypermethylated other CpGs on Ppargc1a and Fasn promoter. This study shed light on the reversibility of phenotypical and epigenetic changes induced by a HFS diet intake.

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Acknowledgments

The authors thank the “Línea Especial” (LE/97, University of Navarra, Spain) for financial support. The technical assistance of Almudena Aguado and Alexandra Claire Simpson is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Nutrition, Food Science and Physiology, University of Navarra, c/ Irunlarrea 1, 31008, Pamplona, Spain

    G. Uriarte, L. Paternain, F. I. Milagro, J. A. Martínez & J. Campion

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  1. G. Uriarte
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  2. L. Paternain
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  3. F. I. Milagro
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Correspondence to J. Campion.

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Figure 1

a Nucleotide sequence of the CpG island in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Ppargc1a) promoter region showing individual CpG dinucleotides. b The effect of HFS diet intake and shifting to a chow diet in the methylation levels of individual CpG dinucleotides in the Ppargc1a promoter. Data are mean ± SEM. Statistical analyses were performed using one-way ANOVA test and DMS post hoc test. Different letters (a, b, c) indicate significant differences between groups of at least p < 0.05. Ppargc1a, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; HFS, high-fat–sucrose; rest, animals shifted from HFS to chow diet; Chr., chromosome; NA, not available (PDF 114 kb)

Figure 2

a Nucleotide sequence of the CpG island in the leptin promoter region showing individual CpG dinucleotides. b The effect of HFS diet intake and shifting to a chow diet in the methylation levels of individual CpG dinucleotides in the leptin promoter. Data are mean ± SEM. Statistical analyses were performed using one-way ANOVA test and DMS post hoc test. Different letters (a, b) indicate significant differences between groups of at least p < 0.05. t indicates a trend to significance. HFS, high-fat–sucrose; rest, animals shifted from HFS to chow diet; Chr., chromosome; NA, not available (PDF 147 kb)

Figure 3

a Nucleotide sequence of the CpG island in the sterol regulatory element-binding transcription factor 1 (Srebf1) promoter region showing individual CpG dinucleotides. b The effect of HFS diet intake and shifting to a chow diet in the methylation levels of individual CpG dinucleotides in the Srebf1 promoter. Data are mean ± SEM. Statistical analyses were performed using one-way ANOVA test and DMS post hoc test. Different letters (a, b) indicate significant differences between groups of at least p < 0.05. t indicates a trend to significance. HFS, high-fat–sucrose; rest, animals shifted from HFS to chow diet; Chr., chromosome; NA, not available (PDF 131 kb)

Figure 4

a Nucleotide sequence of the CpG island in the Fatty acid synthase (Fasn) promoter region showing individual CpG dinucleotides. b The effect of HFS diet intake and shifting to a chow diet in the methylation levels of individual CpG dinucleotides in the Fasn promoter. Data are mean ± SEM. Statistical analyses were performed using One-way ANOVA test and DMS post hoc test. Different letters (a, b) indicate significant differences between groups of at least p < 0.05. HFS, high-fat–sucrose; rest, animals shifted from HFS to chow diet; Chr., chromosome; NA, not available (PDF 135 kb)

Figure 5

a Nucleotide sequence of the CpG island in the Aquaporin 7 (Aqp 7) promoter region showing individual CpG dinucleotides. b The effect of HFS diet intake and shifting to a chow diet in the methylation levels of individual CpG dinucleotides in the Aqp 7 promoter. Data are mean ± SEM. Statistical analyses were performed using one-way ANOVA test and no statistically significant changes were observed. HFS, high-fat–sucrose; rest, animals shifted from HFS to chow diet; Chr., chromosome; NA, not available (PDF 111 kb)

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Uriarte, G., Paternain, L., Milagro, F.I. et al. Shifting to a control diet after a high-fat, high-sucrose diet intake induces epigenetic changes in retroperitoneal adipocytes of Wistar rats. J Physiol Biochem 69, 601–611 (2013). https://doi.org/10.1007/s13105-012-0231-6

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