Premium
SNARK is a Novel Regulator of Muscle Mass and Myocyte Apoptosis
Author(s) -
Lessard Sarah,
Rivas Donato,
So Kawai,
Koh HoJin,
Hirshman Michael,
Fielding Roger,
Goodyear Laurie
Publication year - 2015
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.29.1_supplement.825.19
Subject(s) - skeletal muscle , myocyte , endocrinology , medicine , biology , ampk , sarcopenia , apoptosis , atrophy , muscle atrophy , kinase , microbiology and biotechnology , protein kinase a , genetics
The maintenance of skeletal muscle mass is critical for sustaining health; yet the mechanisms responsible for muscle loss with aging and chronic diseases such as diabetes and obesity are poorly understood. The Snf1‐AMPK‐related kinase (SNARK) belongs to the family of LKB1 substrates known as AMPK‐related kinases. SNARK is expressed in skeletal muscle; however, little is known about SNARK function in this tissue. We found that SNARK expression was increased by muscle cell differentiation in culture. Muscle SNARK expression was also elevated with high‐fat feeding in mice and with aging in humans (78±5 vs 22±1 yr), suggesting that SNARK may function in the regulation of muscle mass. In line with this hypothesis, decreasing endogenous SNARK expression (siRNA) in cultured muscle cells exposed to metabolic stress (250 µM palmitate) caused a 50% reduction in cell viability together with increased caspase activation compared to control conditions, demonstrating that SNARK plays a protective, anti‐apoptotic role in myocyte survival. Likewise, muscle‐specific transgenic animals expressing a SNARK dominant‐negative inactive mutant (SDN) had increased expression and activation of catabolic and apoptotic mediators in skeletal muscles. Moreover, SDN had severe, age‐accelerated muscle atrophy and increased adiposity, consistent with sarcopenic obesity. These data indicate that SNARK protects against age‐related muscle atrophy by inhibiting stress‐induced apoptosis. This investigation identifies a novel role for SNARK in myocyte survival and the maintenance of muscle mass with age. Funding: NIH R01AR42238 (LJG); APS postdoctoral fellowship in Physiological Genomics (SJL).