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Regulation of skeletal muscle p27 and CDK4 expression by high lipid concentrations
Author(s) -
Dungan Cory M,
Jadhav Kavita S,
Willliamson David L
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.942.2
Subject(s) - ceramide , endocrinology , skeletal muscle , medicine , cell cycle , chemistry , myocyte , biology , apoptosis , biochemistry
Obese skeletal muscle has many of the same characteristics as aged muscle, which may suggest premature senescing of obese tissue. High lipid concentrations are a hallmark of obesity, yet little is known about its role on cell cycle. The objectives of these studies were to examine the role of high in vivo and in vitro lipid concentrations on regulators of cell cycle in skeletal muscle. Plantar flexor muscle from C57Bl/6 mice fed a low (10%) or a high (60%) fat diet for 8 wks and C2C12 myoblast cultures treated with a vehicle control or 50μM C2‐ceramide were both analyzed for protein expression of cell cycle regulators. The high fat diet increased (p<.05) body (26%) and liver mass (50%) vs low fat, along with reduced plantar flexor mass/body mass (−16%; p<.05). High fat fed mice had lower (p<.05) protein expression of p27 (−46%) and CDK4 (−25%) vs the low fat. The ceramide treated, insulin‐insensitive myoblasts had reduced CDK4 protein (−60%; p<.05), but no change in p27 vs control. Ceramide increased β‐galactosidase (85%; p<.05) and the proportion of cells in G2‐phase (28%; p<.05), and reduced proliferation (−51%; p<.05) as compared to control. Our results indicate that high lipid concentrations negatively affect muscle growth, which is associated with aberrant G1‐S cell cycle protein expression and a senescent‐like phenotype. Support: University at Buffalo Start Up Funds