Influence of maternal obesity on the multi-omics profiles of the maternal body, gestational tissue, and offspring

Zhao, Duan; Liu, Yusi; Jia, Shanshan; He, Yiwen; Wei, Xiaowei; Liú, Dan; Ma, Wei; Luo, Wenting; Gu, Hui; Yuan, Zhengwei

doi:10.1016/j.biopha.2022.113103

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“…To the best of our knowledge, previous studies on the mechanism of maternal obesity on metabolic disease of offspring are limited ( 27 , 28 ). It has been reported that a high glucose intrauterine environment caused by hyperglycemia in pregnant Sprague-Dawley rats increases risk of insulin resistance in offspring and fatty liver in adulthood ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

lncRNA‑miRNA‑mRNA network in female offspring born from obese dams

et al. 2023

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Maternal obesity is associated with disturbance of lipid metabolism and obesity in offspring; however, the pathogenesis is still unclear. The present study elucidated the role of potential lipid metabolism-associated long non-coding RNA (lncRNA) and identified the pathways involved in mice born to obese dams. In the present study, maternal obesity was induced by feeding a high-fat diet for 10 weeks in female C57/BL6 mice, whereas control mice were fed a standard diet. All female mice mated with healthy male mice and were allowed to deliver spontaneously. The results demonstrated that female offspring from obese dams presented a tendency to become overweight in the first 8 weeks after birth; however, maternal obesity did not significantly alter the body weight of male offspring. RNA-sequencing analysis was performed on female offspring liver at 3 weeks old. Significantly dysregulated lncRNAs and downstream targets in female offspring liver were identified using bioinformatics analysis. lncRNA, microRNA (miRNA or miR) and mRNA expression levels in liver and AML12 cells were assessed using reverse transcription-quantitative PCR. A total of 8 upregulated and 17 downregulated lncRNAs were demonstrated in offspring from obese dams and lncRNA Lockd was indicated to be a key dysregulated lncRNA. Competing endogenous RNA (ceRNA) models suggested that the lncRNA Lockd/miR-582-5p/Elovl5 pathway was key for lipid metabolism in the liver of offspring from obese dams. Finally, small interfering RNA and miRNA inhibitor transfection was used to evaluate the ceRNA models in AML12 cells. Taken together, the results of the present study indicated that lncRNA Lockd-miR-582-5p-Elovl5 network may be disrupted in lipid metabolism and lead to obesity in the offspring of obese dams. This research will provide new insights into the molecular mechanism of obesity and lipid metabolism disorder.

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Section: Discussionmentioning

confidence: 99%