Impaired skeletal muscle hypertrophy signaling and amino acid deprivation response is seen in Apoe KO mice with an unhealthy lipoprotein distribution. Impaired skeletal muscle hypertrophy signaling and amino acid deprivation response is seen in Apoe KO mice with an unhealthy lipoprotein distribution

Background: An impairment of the anabolic response to protein consumption may contribute to sarcopenic development. The current study explore if an unhealthy lipoprotein distribution (LPD) impairs the anabolic and amino acid sensing responses to whey-protein feeding. Methods: Muscle protein synthesis (MPS) was measured by puromycin labeling in Apoe knockout (KO), characterized by an unhealthy LPD, and wild type (WT) mice post-absorptive at 10 and 20 weeks, and post-prandial after whey-protein feeding at 20 weeks. Hypertrophy signaling and amino acid sensing mechanism were studied and gut microbiome diversity explored. Results: Surprisingly, whey-protein did not affect MPS in the post-prandial period. p-mTOR and p-4E-BP1 was increased 2h after whey-protein feeding in both genotypes, but with general lower levels in Apoe KO compared to WT mice. At 20 weeks of age, Apoe KO mice had a greater mRNA-expression for SNAT2, CD98, ATF4 and GCN2 compared to WT-mice. These responses were not associated with gut microbiota compositional differences. Conclusion: Regardless of LPD status muscle protein synthesis was similar in Apoe KO and WT mice. Surprisingly, whey-protein did not stimulate muscle protein synthesis. However, Apoe KO mice had clearly lower levels of hypertrophy signaling, was amino acid deprived, and had impaired amino acid sensing mechanisms.