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. 2024 Jun 19:11:1421848.
doi: 10.3389/fnut.2024.1421848. eCollection 2024.

Effects of maternal advanced lipoxidation end products diet on the glycolipid metabolism and gut microbiota in offspring mice

Wenwen Pang #  1 , Bowei Zhang #  1 , Junshi Zhang  2 , Tianyi Chen  3 , Qiurong Han  3 , Zhen Yang  4
Affiliations

Effects of maternal advanced lipoxidation end products diet on the glycolipid metabolism and gut microbiota in offspring mice

Wenwen Pang et al. Front Nutr. .

Abstract

Introduction: Dietary advanced lipoxidation end products (ALEs), which are abundant in heat-processed foods, could induce lipid metabolism disorders. However, limited studies have examined the relationship between maternal ALEs diet and offspring health.

Methods: To investigate the transgenerational effects of ALEs, a cross-generation mouse model was developed. The C57BL/6J mice were fed with dietary ALEs during preconception, pregnancy and lactation. Then, the changes of glycolipid metabolism and gut microbiota of the offspring mice were analyzed.

Results: Maternal ALEs diet not only affected the metabolic homeostasis of dams, but also induced hepatic glycolipid accumulation, abnormal liver function, and disturbance of metabolism parameters in offspring. Furthermore, maternal ALEs diet significantly upregulated the expression of TLR4, TRIF and TNF-α proteins through the AMPK/mTOR/PPARα signaling pathway, leading to dysfunctional glycolipid metabolism in offspring. In addition, 16S rRNA analysis showed that maternal ALEs diet was capable of altered microbiota composition of offspring, and increased the Firmicutes/Bacteroidetes ratio.

Discussion: This study has for the first time demonstrated the transgenerational effects of maternal ALEs diet on the glycolipid metabolism and gut microbiota in offspring mice, and may help to better understand the adverse effects of dietary ALEs.

Keywords: advanced lipoxidation end products; glycolipid metabolism; gut microbiota; maternal diet; offspring.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XJ declared a past co-authorship with the author BZ to the handling editor.

Figures

Figure 1
Figure 1
Dietary ALEs impaired glycolipid metabolism in dams. (A) The flowchart of this study. (B) IPGTTs of dams. (C) Body weight of dams. (D) AUC of dams. (E) HOMO-IR of dams. (F) Serum insulin level of dams. (G) Serum TC level of dams. (H) Serum TG level of dams. (I) Serum LDL-C level of dams. (J) Serum HDL-C level of dams. (K) Serum leptin level of dams. *p < 0.05, **p < 0.01, Data were expressed as the mean ± SEM.
Figure 2
Figure 2
Maternal ALEs diet impaired glucose metabolism in offspring. (A) Body weight of offspring at birth. (B) Body weight of offspring at weaning. (C) IPGTTs of offspring. (D) AUC of offspring. (E) HOMO-IR of offspring. (F) Serum insulin level of offspring. *p < 0.05, **p < 0.01, Data were expressed as the mean ± SEM.
Figure 3
Figure 3
Maternal ALEs diet impaired lipid metabolism in offspring. (A) Serum TC level of offspring. (B) Serum TG level of offspring. (C) Serum LDL-C level of offspring. (D) Serum HDL-C level of offspring. (E) Serum leptin level of offspring. (F) Representative images of H&E-stained and AB-PAS stained liver tissue (200×, bar = 50 μm). *p < 0.05, **p < 0.01, Data were expressed as the mean ± SEM.
Figure 4
Figure 4
Maternal ALEs diet regulated the AMPK/mTOR/PPARα signaling pathway. (A) Protein expression measured by Western blot. (B) Protein expression of AMPK and mTOR in the liver. (C) Protein expression of PPARα, PKM2 and IRS-1 in the liver. *p < 0.05, **p < 0.01, Data were expressed as the mean ± SEM.
Figure 5
Figure 5
Maternal ALEs diet influenced the expression of TLR4/TRIF/TNF-α proteins. (A) Protein expression measured by Western blot. (B) Protein expression of TLR4, TRIF and TNF-α in the liver. *p < 0.05, **p < 0.01, Data were expressed as the mean ± SEM.
Figure 6
Figure 6
Maternal ALEs diet altered structures and composition of gut microbiota in offspring. (A) Venn diagram of the OTUs. (B) Shannon index of alpha diversity. (C) PCoA plots of gut communities. (D) PC1 and PC2 index of beta diversity. (E) Relative abundance of the bacterial population at the phylum level. (F) Relative abundance of the bacterial population at the genus level. *p < 0.05.
Figure 7
Figure 7
Key bacteria altered by the maternal ALEs diet in offspring (A,B). LEfSe analysis of the gut microbiota from the phylum level to the genus level with LDA values of 4.0. (C) Wilcoxon rank-sum test bar plot on the phylum and genus level. *p < 0.05, **p < 0.01.
Figure 8
Figure 8
Metabolic pathways of bacterial communities by the KEGG pathway database in offspring. (A) Comparison of the HALEs and CON groups. (B) Comparison of the LALEs and CON groups. *p < 0.05, **p < 0.01.
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