Protein malnutrition during infancy has long-lasting consequences on the organism, including stunted growth and metabolic dysfunction. Studies in rodents have shown that growth and metabolism are differentially regulated in males and females. However, the sex-dependent effects of juvenile protein malnutrition have only been sparsely investigated.
Using a mouse model of juvenile malnutrition, we tested the hypothesis that the physiological response to protein scarcity is sex-dependent. Malnourished male mice were stunted and wasted with consistent alterations of the somatotropic axis. On the contrary, malnourished females displayed minimal weight and size growth retardation. In addition, the energy balance was completely dysregulated in response to malnutrition in males but to a much lesser extend in females. Liver transcriptomic analysis further confirmed that the metabolic adaptation to protein malnutrition is sexually dimorphic and revealed that males and females respond to malnutrition by regulating distinct metabolic pathways. However, the apparent adaptation of females to low-protein feeding comes at the expense of an optimal sexual maturation. Indeed, malnourished females display a disrupted puberty. In contrast, the sexual maturation of males is unaffected by malnutrition. We are hypothesizing that this sex-dependent trade off in response to juvenile protein malnutrition is mediated by the hepatokine Fibroblast Growth Factor 21. My PhD work demonstrates that juvenile mice differentially allocate their energy resources in response to protein malnutrition depending on their sex, with males investing in sexual maturation and females in growth and metabolic maturation.
Gratuit
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