Although
weight loss ameliorates many of the metabolic abnormalities associated with
obesity, there has been reluctance to prescribe
weight loss in obese, older individuals because of the fear that it will cause debilitating loss of muscle mass and impair physical function. To gain insight into the mechanisms responsible for the
weight loss-induced changes in muscle mass, we measured the rate of
muscle protein synthesis (by using stable
isotope labeled tracer methodology) during basal, postabsorptive conditions and during mixed meal ingestion in eight obese, older adults: (i) before
weight loss therapy, (ii) ~3 months after starting the
weight loss intervention (i.e., during the active
weight loss phase), when subjects had lost ~7% of their initial
body weight, and (iii) after they had lost ~10% of their
body weight and maintained this new
body weight for ~6 months (~12 months after starting the
weight loss intervention). The basal
muscle protein fractional synthesis rate (FSR) was not affected by
weight loss. Mixed meal ingestion stimulated the rate of
muscle protein synthesis, and the anabolic response (i.e., increase in the
protein synthesis rate above basal values) was greater (P < 0.05) during negative energy balance and active
weight loss at 3 months (0.033 ± 0.012%·per hour, mean ± s.e.m.) than during weight maintenance before and at 12 months of
weight loss therapy (0.003 ± 0.003 and 0.008 ± 0.012%·per hour, respectively). We conclude that during dietary calorie restriction and
weight loss in older adults, the rate of
muscle protein synthesis is not impaired. Thus, the loss of muscle mass must be mediated predominately by adverse effects of dietary calorie restriction on muscle proteolysis.