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. 2023 Jun 23:2023:6540585.
doi: 10.1155/2023/6540585. eCollection 2023.

High-Fat Diet Promotes Adipogenesis in Offspring Female Rats Induced by Perinatal Exposure to 4-Nonylphenol

Hongyu Zhang  1 , Weiran Ke  2 , Xi Chen  3 , Yu Han  1 , Yan Xiong  1 , Feng Zhu  1 , Yang Xiang  1 , Rong Yan  1 , Hongbo Cai  1 , Shunmei Huang  4 , Xiaoyu Ke  5
Affiliations

High-Fat Diet Promotes Adipogenesis in Offspring Female Rats Induced by Perinatal Exposure to 4-Nonylphenol

Hongyu Zhang et al. Biomed Res Int. .

Abstract

Background: Both high-fat diet (HFD) and 4-nonylphenol (4-NP) could affect fat formation in adipose tissue individually. We investigated whether HFD promote abnormal adipose tissue formation caused by early exposure to 4-NP in life and preliminarily explore the possible mechanisms involved.

Methods: The first-generation rats were treated with HFD on postnatal day after pregnant rats exposure to 5 ug/kg/day 4-NP. Then, the second generation rats started to only receive normal diet without 4-NP or HFD. We analyzed organ coefficient and histopathology of fat tissues, biochemical index, and gene level involved in lipid metabolism in female offspring rats.

Results: HFD and 4-NP interaction synergistically increased birth weight, body weight, and organ coefficients of adipose tissue in offspring female rats. HFD accelerately aggravated abnormal lipid metabolism and increased the adipocyte mean areas around the uterus of the offspring female rats induced by prenatal exposure to 4-NP. HFD also facilitate the regulation of gene expression involved lipid metabolism in offspring female rats induced by perinatal exposure to 4-NP, even passed on to the second generation of female rats. Moreover, HFD and 4-NP interaction synergistically declined the gene and protein expression of estrogen receptor (ER) in the adipose tissue of second-generation female rats.

Conclusion: HFD and 4-NP synergistically regulate the expression of lipid metabolism genes in adipose tissue of F2 female rats and promote adipose tissue generation, leading to obesity in offspring rats, which is closely related to low expression of ER. Therefore, ER genes and proteins may be involved in the synergistic effect of HFD and 4-NP.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Experimental design and intervention methods.
Figure 2
Figure 2
The effect of HFD and 4-NP on gestation days, little size, and sex ratio of offspring rats of F1 and F2 offspring rats. HFD and 4-NP interaction had a synergistic effect on the birth weight of F2 offspring rats. ∗P < 0.05 vs. control; #synergistic effect existed.
Figure 3
Figure 3
The pathomorphology change of adipose tissues around the uterus in F1 and F2 female rats (×40). HFD and 4-NP had a synergistic effect on adipocyte mean area around the uterus in offspring female rats. Note: ∗P < 0.05 vs. control; ∗∗P < 0.01 vs. control; #synergistic effect existed.
Figure 4
Figure 4
The effect of HFD and 4-NP on the gene expression of adipose tissue in F1 and F2 female rats. (a) HFD and 4-NP interaction synergistically regulated gene expression involved lipid metabolism in F1 female rats. (b) HFD and 4-NP interaction synergistically regulated gene expression involved lipid metabolism in F2 female rats.
Figure 5
Figure 5
The effect of HFD and 4-NP on the mRNA expression of adipose tissue in F1 and F2 female rats. HFD and 4-NP interaction synergistically upregulated mRNA level of Fas, Lpl, Ppar-γ, and Srebp-1 in F1 and F2 female rats. ∗P < 0.05 vs. control-ND; ∗∗P < 0.01 vs. control-ND; #synergistic effect existed.
Figure 6
Figure 6
The effect of HFD and 4-NP on the expression of ERα in the fatty tissue around the uterus of F2 female rats. HFD and 4-NP interaction synergistically reduce the gene and protein expression of ERα in adipose tissue of F2 female rats. ∗P < 0.05 vs. control-ND; ∗∗P < 0.01 vs. control-ND; #synergistic effect existed.
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