Early life nutritional metabolic programming for later life metabolic health - the nutritional power of galactose

Nutritional interventions in early life, ranging from conception, pregnancy, and lactation into early-life post-weaning periods, the so-called first 1,000 days of human life, can result in long-lasting metabolic health effects in adulthood. This is called nutritional or metabolic programming. The sugar galactose is mainly found in milk as part of milk sugar, lactose. After weaning, the galactose consumption decreases dramatically. It was shown that extended breastfeeding has beneficial effects, however, the contribution of galactose is not clear. Therefore, we aim to study whether galactose intake in early life has long-lasting effects on metabolic health in later life.

Project description

We are using two different models, a mouse model and a drosophila model to study the programming effects of galactose, as metabolic molecular pathways are highly conserved. In mice, we aim to investigate whether partial replacement of glucose with galactose in early life can protect mice against high-fat diet-induced obesity in later life. As an example, 16 en% glucose is replaced with 16 en% galactose in the postweaning diet for three weeks, and then all mice receive the same obesogenic high-fat diet for nine weeks. We focus on the programming effects of galactose on physiological parameters like body composition, energy expenditure, insulin sensitivity and hormone homeostasis, and metabolic parameters including molecular regulation of e.g. gene expression.

In Drosophila melanogaster, fruit flies, we aim to investigate what are the metabolic consequences of galactose in Drosophila, and whether galactose intervention in early life has long-lasting effects on lifespan and metabolic health in later life. As an example, different dosages of galactose in early life (during the larval period) are given, and thereafter they receive the same (obesogenic) diets in later life (after eclosion). We are interested in the direct effect of galactose on development and other physiological and metabolic parameters together with the programming effects on lifespan and an array of physiological and metabolic parameters, etc.

Results

In one of our mice studies, we found the partial replacement of glucose with galactose in an early-life post-weaning diet significantly increased white adipose tissue Adiponectin expression and serum adiponectin levels in later life without alterations in fat mass, and decreased skeletal muscle Irs2 expression in female mice, two parameters indicating improved later-life health (Sun et al., IJMS 2022).