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Effect of altered AMP‐activated protein kinase activity and exercise training on muscle PBEF‐1/visfatin levels.
Author(s) -
Brandauer Josef,
Koh HoJin,
Jung Michelle M.,
Toyoda Taro,
An Ding,
Yu Haiyan,
Fujii Nobuharu,
Hirshman Michael F.,
Witters Lee A.,
Goodyear Laurie J.
Publication year - 2008
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.22.1_supplement.754.7
Subject(s) - ampk , skeletal muscle , endocrinology , medicine , protein kinase a , amp activated protein kinase , cardiac muscle , genetically modified mouse , chemistry , myocyte , sirtuin 1 , transgene , biology , phosphorylation , biochemistry , downregulation and upregulation , gene
Pre‐B‐cell enhancing factor 1 (PBEF‐1; also known as visfatin) is a stress‐inducible regulator of intracellular NAD+. Elevated NAD+ levels are associated with increased Sirtuin activity, which can contribute to life span extension in some organisms. Caloric restriction may serve to extend life span via this mechanism. Since AMP‐activated protein kinase (AMPK) serves an important role as a cellular fuel gauge, we investigated the role of AMPK in regulating muscle PBEF‐1 levels. PBEF‐1 was significantly increased (50%) in tibialis anterior muscle from mice expressing an activating mutation of AMPK (γ1R70Q) in skeletal muscle (p<0.01). PBEF‐1 was significantly decreased in the muscles of two models of impaired AMPK activity, muscle‐specific AMPKα2 inactive transgenic mice (13%; P<0.05) and muscle‐specific LKB1 knockout mice (30%; p<0.01). In addition to skeletal muscle, PBEF‐1 was also decreased in cardiac tissue from the AMPKα2 inactive transgenic mice and LKB1 knockouts, and this effect was relatively greater in the heart compared to skeletal muscle. We next investigated the effects of seven weeks of voluntary wheel cage running on PBEF‐1 protein expression in skeletal muscle and heart from rats. Training resulted in 26% increased PBEF‐1 levels in cardiac muscle (p<0.05), but had no effect in triceps muscle despite clearly increased citrate synthase activity in this muscle. In conclusion, AMPK may be an important regulator of the purported anti‐aging protein, PBEF‐1 in skeletal and cardiac muscles. PBEF‐1 levels are significantly elevated after training in cardiac muscle, suggesting a previously unidentified potential aging‐protective role of chronic exercise in the heart.