Skeletal Muscle Changes in Obese, Older Women following Six Months of Exercise and Caloric Restriction

Abstract

Dietary interventions involving caloric restriction lead to weight loss, however this loss typically consists of both adipose tissue and skeletal muscle. The loss of skeletal muscle is of significant concern for older adults since it can directly contribute to functional disability. Exercise may effectively preserve skeletal muscle mass and function during weight loss, but limited data are available regarding the cellular mechanisms underlying this outcome. PURPOSE: To evaluate the effects of a weight loss intervention including exercise and caloric restriction on molecular indices relevant to mitochondrial biogenesis and autophagy within skeletal muscle of obese, older women. METHODS: Obese, older women (N=27, 63.8 ± 5.9 yr, BMI>28 kg/m2) with mild to moderate functional impairment were randomly assigned to participate in either a six-month weight loss intervention including a weight loss + exercise intervention (WL+E) or an educational control group (CON). In the WL+E condition participants were instructed to reduce their caloric intake by ∼500-1000 kcal/day and engage in structured exercise training that included mild to moderate intensity walking and lower body resistance exercises. A subset of participants (n=12) volunteered to undergo percutaneous biopsy of the vastus lateralis. Muscle samples were assayed via western blot and QPCR to determine content of proteins and mRNAs relevant to mitochondrial biogenesis and autophagy. Changes in expression were examined using fold changes where values > 1 indicate increased expression and values < 1 indicate decreased expression. Expression changes were analyzed statistically by independent samples T-tests (proteins) or Mann-Whitney tests (mRNA). RESULTS: Compared to CON, WL+E resulted in significant (p < 0.05) increases in expression of several genes relevant to both mitochondrial biogenesis (PGC1·, TFAM) and autophagy (Atg7, LC3B, and Lamp2). Expression of each of these genes increased 2-3 fold in WL+E and declined in CON (0.4-0.55 fold). Additionally, muscle content of mitochondrial TFAM protein increased 1.41 + 0.12 (mean + SE) fold in the WL+E, compared to a slight decline in CON (0.93 + 0.07 fold, p=0.03). CONCLUSION: Weight loss interventions that include exercise may preserve muscle mass in obese, older women at least partially by altering molecular signaling related to two key mechanisms that govern myocyte quality - mitochondrial biogenesis and autophagy. Supported by the Claude D. Pepper Older Americans Independence Center (1P30AG028740-01) and the University of Florida Opportunity Fund.