On obesogenic diet exposure of parents and sex-specific programming of overweight in mouse offspring

Abstract

Abstract Background/Objectives: Whether parental obesity alters the probability that a child will become an obese adult is not fully understood. Thus, we were interested in exploring how parents’ obesity status influence their offspring’s weight. We further asked whether exposure to milder forms of maternal or paternal obesity during early developmental stages induces programming of long-term overweight in offspring, and if this effect may be sex specific. Subjects/Methods: We randomly assigned three-week-old mice to two groups, one group receiving a high-fat diet (HFD), the other group receiving a control diet (CD). Adult females of both groups were mated to males fed with HFD or CD. Each group consisted of four females and two males (one female deceased). Interventions/methods: After analysing weight gain trajectories of parental (P) and filial (F1) individuals, we investigated F1 transcriptome assay data from four tissues (liver, epigonal visceral, inguinal subcutaneous, and interscapular brown adipose tissue) of 15 male offspring in relation to their parents’ obesity status. Results DEGs were only considered significant when false discovery rate adjusted p values were p < 0.05, and the log2-fold change was at least 1. In brown adipose tissue of male offspring with both parents being obese, when compared to males with only a father obese, expression patterns suggested a higher degree of insulin resistance, impaired muscle growth and regeneration, altered impulse control, and possibly, protection against diet–induced obesity. In liver, the contrast between offspring to obese parents and those to not-obese parents was characterized by expression differences related to fatty acid metabolism, water homeostasis, inflammation and others. Conclusions We provide transcriptomic support for the hypothesis that having two obese parents, rather than having only one obese parent, further amplifies risks for obesity and metabolic disease among males.