Abstract
Guidelines advising pregnant women to avoid food and beverages with high fat and sugar have led to an increase in the consumption of “diet” options sweetened by artificial sweeteners (AS). Yet, there is limited information regarding the impact of AS intake during pregnancy on the long-term risk of cardiometabolic and reproductive complications in adult offspring. This study examined the influence of maternal acesulfame-K (Ace-K) and fructose consumption on metabolic and reproductive outcomes in offspring. Pregnant C57BL/6 mice received standard chow ad-libitum with either water (CD), fructose (Fr; 20% kcal intake), or AS (AS; 12.5 mM Ace-K) throughout pregnancy and lactation (n = 8/group). Postweaning offspring were maintained on a CD diet for the remainder of the experiment. Body weight, food intake, and water intake were measured weekly. Oral glucose tolerance tests (OGTT) were undertaken at 12 weeks, and the offspring were culled at week 14. Female, but not male, AS groups exhibited decreased glucose tolerance compared to Fr. There was an increase in gonadal fat adipocyte size in male offspring from AS and Fr groups compared to CD groups. In female offspring, adipocyte size was increased in the Fr group compared to the CD group. In female, but not male offspring, there was a trend toward increase in Fasn gene expression in AS group compared to the CD group. Maternal AS and Fr also negatively impacted upon female offspring estrus cycles and induced alterations to markers associated with ovulation. In summary, exposure to Ace-k via the maternal diet leads to impaired glucose tolerance and impacts adipocyte size in a sex-specific manner as well as significantly affecting estrus cycles and related gene markers in female offspring. This has implications in terms of providing tailored dietary advice for pregnant women and highlights the potential negative influence of artificial sweetener intake in the context of intergenerational impacts.
Highlights
The consumption of artificial sweeteners (AS) has increased in recent decades [1, 2], with beverages being a common mode of intake
Despite the promoted beneficial effects of AS, a number of studies have suggested that AS consumption can elevate the risk of insulin resistance (IR), type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease [3,4,5,6], and negatively impact the reproductive system [7, 8]
Maternal AS and Fr consumption had no impact on offspring birth, weaning, or final cull weight in either female or male offspring
Summary
The consumption of artificial sweeteners (AS) has increased in recent decades [1, 2], with beverages being a common mode of intake. It is well established that suboptimal conditions during pregnancy and lactation, including poor maternal nutrition, can have an impact on the risk for development of disorders in offspring, including cardiometabolic disease, obesity [9], and reproductive disorders such as polycystic ovarian syndrome (PCOS) or anovulation in later life [10, 11]. Further studies in mice have shown the presence of Ace-K in the amniotic fluid and the mother’s milk following intraoral feeding, which directly increases male offspring’s sweet-taste preference for Ace-K in adulthood [18] Previous work from this group in mice has demonstrated that maternal AS and fructose (Fr) intake induces maternal metabolic dysfunction and negatively alters fetal development in mice [15]
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