Suboptimal refeeding compensates stunting in a mouse model of juvenile malnutrition

Abstract

BackgroundThe highest rate of growth in mammals occurs in early life, particularly after weaning. Growth is conditioned by the nutritional status. Indeed, restriction of dietary protein in early life leads to wasting and/or stunting.ObjectiveHere, we developed a mouse model of juvenile protein malnutrition triggering stunting and studied the physiological effects of refeeding using various diets and interventions.MethodsIn a first intervention, we refed the mice with an optimal diet (breeding diet, rich in protein and fiber). We then treated the mice during the refeeding phase withLactiplantibacillus plantarumWJL (LpWJL), a previously described bacterial strain that has the ability to stimulate growth via the somatotropic axis in early life upon chronic malnutrition. Finally, we established a model of suboptimal refeeding, upon which the mice were given a western diet (33% kcal from fat; 17% kcal from protein) or an isocaloric modified western diet low in proteins (33% kcal from fat; 8% kcal from protein) after juvenile protein malnutrition.ResultsWe found that, in females, optimal growth was restored by control diet refeeding. In males, control diet refeeding after a five-week protein restriction was not enough to catch up growth retardation. No supplementary beneficial effect was found associated to the microbial intervention in this context. Surprisingly, our results showed that, in males, suboptimal refeeding with a diet rich in fat but low in protein was sufficient to buffer the deleterious effects of protein restriction on growth. However, this macroscopic benefit was associated to metabolic alteration. While LpWJLtreatment had no effect on growth per se, we found that bacterial treatment further impaired glycemic control upon suboptimal refeeding.ConclusionsOverall, we describe a novel model of juvenile protein energy malnutrition, where growth can be caught up by suboptimal refeeding.

Semaglutide interferes with postnatal growth in a diet-dependent manner

“…Samples were kept at −20°C. We decided to restrict our study to male mice because we have previously shown that juvenile malnourished males display a stronger phenotype than malnourished females [24].…”