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Differential response of anabolic signaling with high‐fat feeding and aging in skeletal muscle after insulin stimulation
Author(s) -
McDonald Devin J,
Morris Evan P,
Haran Prashanth H,
Fielding Roger A,
Rivas Donato A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.244.1
Subject(s) - endocrinology , medicine , anabolism , skeletal muscle , insulin resistance , protein kinase b , stimulation , p70 s6 kinase 1 , insulin , biology , phosphorylation , pi3k/akt/mtor pathway , signal transduction , chemistry , microbiology and biotechnology
The increased accumulation of intramyocellular lipids with advancing age and obesity may be a contributing factor to anabolic resistance in skeletal muscle. Aging and obesity have differential causes of fat accumulation in muscle and it is hypothesized they may have divergent mechanisms leading to anabolic resistance. In order to test this hypothesis we used C57BL/6 mice aged 6 months and fed a control diet (YNG CFD, 15% fat/kcal) or a diet high in fat (YNG HFD, 60% fat/kcal) and mice aged 24 months fed a control diet (OLD CFD) for 12 weeks. The animals were then fasted 5 h and were either injected with a single bolus of insulin (INS, 0.85 IU/kg bw) or saline vehicle (SAL) 30 mins before skeletal muscle collection. Western blotting was carried out to detect differences in activation of growth and degradation pathways. The phosphorylation Akt, mTOR and S6K1 were higher with INS in all groups but the magnitude of this change was differentially affected by age and diet. INS did not change the phosphorylation of FOXO1/FOXO4, NFβB and its inhibitor IκBα. However, IκBα phosphorylation, and therefore inactivation, was higher in OLD CFD in SAL and INS groups. Using quantitative PCR we observed a significant difference in the gene expression of NFβB targets, TLR2 and IL1β with aging and diet. We conclude that aging and a high‐fat diet differentially effect growth and degradation pathways in skeletal muscle after insulin stimulation. Grant Funding Source : USDA and NIH/NIA