The proposed studies are designed to determine if protein synthesis, glucose production, and sympathetic nervous system activity are regulators of alterations in resting metabolic rate (RMR) associated with overfeeding, underfeeding, and diabetes. While the nutritional influences on RMR have been assessed (increased RMR with overfeeding, reduced RMR with underfeeding), there is very little information about the mechanisms involved. The available evidence suggests that overfeeding might increase protein synthesis and glucose production, processes that require energy. The effect of overfeeding on RMR (indirect calorimetry), protein synthesis (13C leucine turnover), and glucose production (dideuteroglucose turnover) will be simultaneously determined in lean, obese, and post-obese humans to determine if increases in RMR are correlated with changes in protein synthesis or glucose production, and if obese subjects have smaller increases in these variables than lean subjects. Underfeeding is known to reduce RMR, protein synthesis, glucose production, and serum T3 levels. Studies will be done to determine if preventing the decrease in T3 levels can prevent the decrease in RMR in underfed obese subjects by maintaining protein synthesis and glucose production. RMR, protein synthesis, and glucose production are elevated in diabetic subjects after insulin withdrawal. Studies will be done to determine if the increased RMR and protein synthesis are caused by elevated levels of glucagon, 3-hydroxybutyrate, or leucine, and to examine the effect of treating type II obese diabetic patients with insulin on RMR, protein synthesis, and glucose production. Because the sympathetic nervous system is an important regulator of RMR in animals, the effects of diet and insulin treatment on 3H-norepinephrine turnover and the effect of propranolol on RMR of obese and overfed lean subjects will be assessed.
| Welle, S; Matthews, D E; Campbell, R G et al. (1989) Stimulation of protein turnover by carbohydrate overfeeding in men. Am J Physiol 257:E413-7 |
