A nutritional growth retardation study, which closely resembles the nutritional observations in children who consumed insufficient total energy to maintain normal growth, was conducted. In this study, a nutritional stress in weanling rats placed on restricted balanced diet for 4 weeks is produced, followed by a food recovery period of 4 weeks using two enriched diets that differ mainly in the slow (SDC) or fast (RDC) digestibility and complexity of their
carbohydrates. After re-feeding with the RDC diet, animals showed the negative effects of an early
caloric restriction: an increase in adiposity combined with poorer muscle performance,
insulin resistance and, metabolic inflexibility. These effects were avoided by the SDC diet, as was evidenced by a lower adiposity associated with a decrease in
fatty acid synthase expression in adipose tissue. The improved muscle performance of the SDC group was based on an increase in
myocyte enhancer factor 2D (MEF2D) and
creatine kinase as markers of muscle differentiation as well as better
insulin sensitivity, enhanced
glucose uptake, and increased metabolic flexibility. In the liver, the SDC diet promoted
glycogen storage and decreased
fatty acid synthesis. Therefore, the SDC diet prevents the catch-up fat phenotype through synergistic metabolic adaptations in adipose tissue, muscle, and liver. These coordinated adaptations lead to better muscle performance and a decrease in the fat/lean ratio in animals, which could prevent long-term negative metabolic alterations such as
obesity,
insulin resistance,
dyslipidemia, and liver fat deposits later in life.