Maternal Intake of Either Fructose or the Artificial Sweetener Acesulfame-K Results in Differential and Sex-Specific Alterations in Markers of Skin Inflammation and Wound Healing Responsiveness in Mouse Offspring: A Pilot Study

Abstract

Growing evidence has demonstrated that maternal artificial sweetener (AS) consumption may not be a beneficial alternative when compared to sugar-sweetened beverages and potentially leads to metabolic dysfunction in adult offspring. Compromised skin integrity and wound healing associated with type 2 diabetes can lead to complications such as diabetic pressure injury (PI). In this context, the skin plays an important role in the maintenance of metabolic homeostasis, yet there is limited information on the influence of sugar- or AS-sweetened beverages during pregnancy on developmental programming and offspring skin homeostasis. This study examined the impact of maternal fructose or acesulfame-k consumption on offspring wound healing. Female C57Bl/6 mice received a chow diet ad libitum with either water (CD), fructose (FR; 34.7 mM fructose), or AS (AS; 12.5 mM Acesulfame-K) throughout pregnancy and lactation. PIs were induced in offspring at 9 weeks of age (n = 6/sex/diet). PIs and healthy skin biopsies were collected for later analysis. Maternal AS intake increased skin inflammatory markers in healthy biopsies while an FR diet increased Tgfb expression, and both diets induced subtle changes in inflammatory markers post-wound inducement in a sex-specific manner. Furthermore, a maternal FR diet had a significant effect on pressure wound severity and early wound healing delay, while AS maternal diet had a sex-specific effect on the course of the healing process. This study demonstrates the need for a better understanding of developmental programming as a mediator of later-life skin integrity and wound responsiveness.

The impact of non-nutritive sweeteners on fertility, maternal and child health outcomes: a review of human and animal studies

“…The effects of in utero acesulfame-k and fructose exposure also extended to adult offspring. Female but not male offspring exhibited increased glucose intolerance accompanied by increased adipocyte size and reduced wound healing capacity in both males and females (60,71) . Azad et al (78) also examined the impact of NNS during pregnancy on offspring adipose tissue outcomes.…”

“…While inflammation is a key initiator of labour in term pregnancies, dysregulation of these processes can result in early delivery. While there is some evidence from mechanistic studies that NNS exposure can result in increased inflammation in organs such as the adipose tissue in humans (18) and, (70) skin (71) and liver (45) in animal models, there is no evidence in relation to how sweeteners influence inflammation in the reproductive organs.…”