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Normal-Weight Offspring of Parents With Diet-Induced Obesity Display Altered Gene Expression Profiles

Overview
Journal Obes Sci Pract
Date 2025 Feb 18
PMID 39963593
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Abstract

Objective: A Western diet is associated with obesity, and the link between parental and offsprings' obesity is unclear. Among mice, this study examined how parents' Western diets affect their male offspring's obesity risk. This study further explored whether early exposure to obesogenic diets from either parent influences offsprings' long-term weight gain.

Methods: Three-week-old C57BL6/NTac mice were assigned to a Western diet (WD) or control diet (CD), given from six to 14 weeks old. Adults from these dietary groups were then mated to create four breeding combinations: CD/CD, CD/WD, WD/CD, and WD/WD. Weight gain trajectories were studied in parents (P) and offspring (F1), along with gene expression in four tissues of male offspring. Non-linear mixed effect modeling and q-mode PCA were used to assess the influence of sex, litter size, and parental diet on gene expression, before describing gene expression in more detail.

Results: Offsprings' weight gain was mainly influenced by sex and litter size, with no significant impact from parental diet. At the same time, gene expression differences among offspring, particularly between WD/WD and CD/CD offspring, were linked to genes associated with inflammation, stress response, and other obesity-relevant processes.

Conclusions: Obegenesic diet of two parents with obesity, rather than only one, likely alters the risks of metabolic disease in male mice even at normal weights.

References
1.
Maharjan B, McLennan S, Yee C, Twigg S, Williams P . The Effect of a Sustained High-Fat Diet on the Metabolism of White and Brown Adipose Tissue and Its Impact on Insulin Resistance: A Selected Time Point Cross-Sectional Study. Int J Mol Sci. 2021; 22(24). PMC: 8706763. DOI: 10.3390/ijms222413639. View

2.
Yoshinari K, Takagi S, Yoshimasa T, Sugatani J, Miwa M . Hepatic CYP3A expression is attenuated in obese mice fed a high-fat diet. Pharm Res. 2006; 23(6):1188-200. DOI: 10.1007/s11095-006-0071-6. View

3.
Hasegawa Y, Chen S, Sheng L, Jena P, Kalanetra K, Mills D . Long-term effects of western diet consumption in male and female mice. Sci Rep. 2020; 10(1):14686. PMC: 7477228. DOI: 10.1038/s41598-020-71592-9. View

4.
Feng D, Tang Y, Kwon H, Zong H, Hawkins M, Kitsis R . High-fat diet-induced adipocyte cell death occurs through a cyclophilin D intrinsic signaling pathway independent of adipose tissue inflammation. Diabetes. 2011; 60(8):2134-43. PMC: 3142076. DOI: 10.2337/db10-1411. View

5.
Boyle E, Weng S, Gollub J, Jin H, Botstein D, Cherry J . GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics. 2004; 20(18):3710-5. PMC: 3037731. DOI: 10.1093/bioinformatics/bth456. View