Smaller Muscle Mass in Obese Zucker Rats is not caused by Mitochondrial-Associated Apoptosis in Skeletal Muscle

Abstract

INTRODUCTION The obese zucker rat (OZR) is a good model of insulin resistance and Type 2 diabetes. It has been reported that OZR have reduced skeletal muscle mass when compared to the lean zucker rat (LZR) (Durschlag RP and Layman DK. Skeletal muscle growth in lean and obese Zucker rats. Growth 47: 282–291, 1983). Skeletal muscle apoptosis has been shown to be a contributing factor in age related muscle loss and sarcopenia (Deschenes MR. Effects of aging on muscle fibre type and size. Sports Med 34: 809–824, 2004; Alway SE et al. Potential role for Id myogenic repressors in apoptosis and attenuation of hypertrophy in muscles of aged rats. Am J Physiol Cell Physiol 283: C66-C76, 2002). In addition, apoptosis has been demonstrated in cardiac tissue in Type 2 diabetes (Frustaci A, et al. Myocardial cell death in human diabetes. Circ Res 87: 1123–1132,2000). PURPOSE: The purpose of this study was to investigate whether apoptosis contributes to decreased skeletal muscle mass in the OZR. METHODS: The medial gastrocnemius muscle of 7 OZR and 7 LZR (20–22 weeks old) were collected. Mitochondrial-associated apoptosis signaling was determined by measurement of Cytochrome-C in mitochondria-free cytosolic fractions, and through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). In addition Bax and Bcl-2 mRNA and protein content were determined. RESULTS: The medial gastrocnemius was 19% smaller in the OZR compared to lean LZR (33.92 +[[Unsupported Character – Codename ­]] 1.81 vs. 42.14 +2.33 g/mm tibial length). There was no difference in cytosolic Cytochrome-C or the number of TUNEL positive nuclei (<1 nuclei per 100 fibers examined) between OZR and LZR groups. In addition, the Bax and Bcl-2 mRNA and protein content were similar between OZR and LZR animals. CONCLUSIONS Mitochondrial signaling for apoptosis in skeletal muscle was not different between 20–22 week old OZR and LZR rats. Mitochondrial-associated apoptosis does not appear to contribute to decreased muscle size in this model of insulin resistance. Funded by NIH: NIA Grant R01AG021530.