Examination of the effect of chronic high sucrose diet and associated intergenerational effect on metabolic and endocrine health in C57BL/6N mice

Abstract

Although the mainstream view is that high added sugar consumption leads to obesity and related diseases, controversies exist. This Ph.D. project is the first of its kind to study the effects of chronic high sucrose consumption on metabolic and endocrine health over 2 generations in mammals, including a comparison between different patterns of parental sugar consumption. The first study investigated the effect of chronic ad libitum consumption of high sucrose (25% daily kcal) vs. sucrose-free and low (10% daily kcal) sucrose diets on metabolic and endocrine health in the F0 generation. Results showed that although chronic high sugar consumption led to overeating compared to sugar-free and low sugar diets (pmixed = 0.0022 & 0.0246 for 25% vs. 0% and 10%, respectively) in females, there was no weight gain [pmixed = 0.0460 & 0.4216 for 25% vs. 0% and 10% (25% < 0% & 10%), respectively] and fat accumulation [pmixed = 0.0012 & 0.3701 for 25% vs. 0% and 10% (25% < 0% & 10%), respectively]. However, overeating (pmixed = 0.0309, 25% vs. 10%) and obesity (pmixed = 0.0215, 25% vs. 0%) was observed in males. There was also no disrupted carbohydrate metabolism (e.g., fasting insulin: pANOVA = 0.639 & 0.753 for 25% vs. 0% and 10%, respectively). However, IL-6 level was higher in males on a high sugar diet (pmixed = 0.0118 & 0.0028 for 25% vs. 0% and 10%, respectively). The second study assessed the intergenerational effect of an ad libitum low (10% daily kcal) vs. high (25% daily kcal) sucrose diet in F0 mice on the metabolic and endocrine health of their offspring (F1), and the effect of chronic consumption of 10% vs. 25% kcal sucrose diet on health in F1 mice. Results suggested that compared to offspring born to both parents consuming a low sugar diet or with one parent consuming a high sugar diet, chronic high sugar intake by both parents did not lead to obesity (pmixed = 0.0147, LL/L > HH/L), disrupted carbohydrate metabolism (e.g., fasting glucose: pmixed = 0.0439, LH/L > HH/L), and inflammation (e.g., TNF-α: pmixed = 0.0001, HL/H > HH/H) in offspring. Moreover, there were overall no differences in outcomes between offspring with maternal and paternal high sugar intake (e.g., body fat: pmixed = 0.7069, LH/L vs. HL/L), which highlights the importance of paternal diet in influencing offspring health. Additionally, long-term high sugar consumption by offspring generally did not harm health compared with low sugar consumption (e.g., fasting insulin: pANOVA = 0.211, HH/H vs. HH/L). There were also interactions between parental and offspring diets (e.g., high sucrose intake by both parents seemed to cause less adiposity compared with others only when offspring consumed a low sucrose diet). Overall, this project suggests that although chronic high sugar intake may not induce obesity and related disturbances in parents, there could be an intergenerational effect that is shaped by the concept of ‘intergenerational plasticity’. Future studies should investigate the health effects of high sugar intake across generations on larger sample sizes over a longer period.