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.