Semester

Spring

Date of Graduation

2008

Document Type

Dissertation

Degree Type

PhD

College

School of Medicine

Department

Physiology, Pharmacology & Neuroscience

Committee Chair

Randall W. Bryner.

Abstract

The Obese zucker rat (OZR) is a model of obesity and metabolic syndrome, with a reduced skeletal muscle mass compared with the lean zucker rat (LZR). Growth and hypertrophy of muscle fibers critically depend on activation and differentiation of satellite cells into new myonuclei, as well as the prevention of myonuclear apoptosis. Akt is known to regulate satellite cell activation and differentiation and inhibit apoptotic signaling. Akt activity is also reduced in the OZR compared to the LZR. The present study had two primary purposes; first, to observe, in vitro, the effects of the saturated free fatty acid palmitate on C2C12 mouse myoblast proliferation and differentiation, Akt signaling and apoptosis in myotubes, and second, to examine if there was reduced Akt signaling, satellite cell proliferation and differentiation, and/or increased satellite death in the OZR compared to the LZR. Akt signaling was significantly reduced both in vitro following palmitate treatment and in vivo in the OZR. Furthermore, myoblast proliferation and differentiation were reduced after palmitate treatment, in vitro, and satellite cell activation was reduced in the OZR compared to the LZR. Although palmitate treatment was sufficient to induce apoptotic signaling in C2C12 myotubes, there was no increase in apoptotic signaling in muscles of the OZR. Together, these data indicate that although disruptions in Akt signaling in muscles of the OZR may be responsible for the decrease in muscle mass through attenuated satellite cell activation and proliferation, increased apoptotic signaling does not appear to be a factor to explain the decrease muscle mass in the OZR compared to the LZR.

Download

Share

COinS