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High-Fat Diet Regulation of Cell Cycle

Abstract

Dungan, C. M. and Williamson, D. L. University at Buffalo, Buffalo, NY

Purpose: Like aged individuals, skeletal muscle proliferative capacity, mass, and function of the obese are decreased. This has a negative metabolic impact, because skeletal muscle is a major site for insulin action and glucose disposal and comprises a large portion of fat free mass, which is positively associated with metabolic homeostasis. There is mounting evidence of increased expression of senescence proteins in obese tissues, similar to that of aged, suggesting premature senescing of obese tissue. The aim of this study was to determine if cell cycle regulatory proteins (p53, p21, p27, Rb, and E2F1) are altered in young and old rodents following consumption of a high-fat diet. Methods: 3-month (Y) and 23-month (O) male mice were fed either a 10% (LF) or 60% (HF) lard-containing diet for 8 and 6 weeks, respectively, that resulted in 25% and 30% increase in body weight (vs. respective LF group). Following the treatment period, the plantar flexor complex (gastrocnemius, plantaris, soleus) was removed and processed to obtain total, nuclear, and cytosolic fractions. Results: Nuclear and cytosolic p21 expression was significantly reduced (pConclusion: Consumption of a high-fat diet that results in obesity, significantly alters cell cycle regulatory proteins in both young and old muscle, which may indicate potential mechanisms for reduced muscle adaptation in the aged and/or obese.

Research was supported by UB Start-Up Funds

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