Impaired skeletal muscle hypertrophy signaling and amino acid deprivation response in Apoe knockout mice with an unhealthy lipoprotein distribution
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Impaired skeletal muscle hypertrophy signaling and amino acid deprivation response in Apoe knockout mice with an unhealthy lipoprotein distribution. / Agergaard, Jakob; Zillmer, Mie Cecilie Faber; Castro-Mejía, Josué L.; Mertz, Kenneth; Kot, Witold; Højfeldt, Grith; van Hall, Gerrit; Nielsen, Dennis S.; Schjerling, Peter; Holm, Lars.
I: Scientific Reports, Bind 11, 16423, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Impaired skeletal muscle hypertrophy signaling and amino acid deprivation response in Apoe knockout mice with an unhealthy lipoprotein distribution
AU - Agergaard, Jakob
AU - Zillmer, Mie Cecilie Faber
AU - Castro-Mejía, Josué L.
AU - Mertz, Kenneth
AU - Kot, Witold
AU - Højfeldt, Grith
AU - van Hall, Gerrit
AU - Nielsen, Dennis S.
AU - Schjerling, Peter
AU - Holm, Lars
N1 - Publisher Copyright: © 2021, The Author(s).
PY - 2021
Y1 - 2021
N2 - This study explores if unhealthy lipoprotein distribution (LPD) impairs the anabolic and amino acid sensing responses to whey-protein feeding. Thus, if impairment of such anabolic response to protein consumption is seen by the LPD this may negatively affect the skeletal muscle mass. Muscle protein synthesis (MPS) was measured by puromycin labeling in Apolipoprotein E knockout (Apoe KO), characterized by an unhealthy LPD, and wild type mice post-absorptive at 10 and 20 weeks, and post-prandial after whey-protein feeding at 20 weeks. Hypertrophy signaling and amino acid sensing mechanisms were studied and gut microbiome diversity explored. Surprisingly, whey-protein feeding did not affect MPS. p-mTOR and p-4E-BP1 was increased 2 h after whey-protein feeding in both genotypes, but with general lower levels in Apoe KO compared to wild type. At 20 weeks of age, Apoe KO had a greater mRNA-expression for SNAT2, CD98, ATF4 and GCN2 compared to wild type. These responses were not associated with gut microbiota compositional differences. Regardless of LPD status, MPS was similar in Apoe KO and wild type. Surprisingly, whey-protein did not stimulate MPS. However, Apoe KO had lower levels of hypertrophy signaling, was amino acid deprived, and had impaired amino acid sensing mechanisms.
AB - This study explores if unhealthy lipoprotein distribution (LPD) impairs the anabolic and amino acid sensing responses to whey-protein feeding. Thus, if impairment of such anabolic response to protein consumption is seen by the LPD this may negatively affect the skeletal muscle mass. Muscle protein synthesis (MPS) was measured by puromycin labeling in Apolipoprotein E knockout (Apoe KO), characterized by an unhealthy LPD, and wild type mice post-absorptive at 10 and 20 weeks, and post-prandial after whey-protein feeding at 20 weeks. Hypertrophy signaling and amino acid sensing mechanisms were studied and gut microbiome diversity explored. Surprisingly, whey-protein feeding did not affect MPS. p-mTOR and p-4E-BP1 was increased 2 h after whey-protein feeding in both genotypes, but with general lower levels in Apoe KO compared to wild type. At 20 weeks of age, Apoe KO had a greater mRNA-expression for SNAT2, CD98, ATF4 and GCN2 compared to wild type. These responses were not associated with gut microbiota compositional differences. Regardless of LPD status, MPS was similar in Apoe KO and wild type. Surprisingly, whey-protein did not stimulate MPS. However, Apoe KO had lower levels of hypertrophy signaling, was amino acid deprived, and had impaired amino acid sensing mechanisms.
U2 - 10.1038/s41598-021-96000-8
DO - 10.1038/s41598-021-96000-8
M3 - Journal article
C2 - 34385572
AN - SCOPUS:85112509098
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 16423
ER -
ID: 276752169