Improving skeletal muscle health is an important component of obesity treatment. Apart from locomotion, skeletal muscle tissue is fundamental for the regulation of macronutrient metabolism during the postprandial period, which is precisely where metabolic derangements are most often observed. In order for the skeletal muscle to adapt and retain its capacity for high throughput of macronutrients, damaged proteins must be degraded and replaced on a continual basis. Moreover, amino acids from meals are crucial for the muscle to replace those lost for other needs (e.g. gluconeogenesis and oxidation). Skeletal muscle appears to be more responsive to amino acid replacement in normal-weight than the muscle of obese individuals. However, no studies have assessed the impact of obesity on the muscle protein synthetic response to the fundamental anabolic stimuli (muscle contraction, protein ingestion) to human skeletal muscle tissue. Previous studies of obesity and muscle protein metabolism have employed intravenous amino acid infusions, which do not accurately reflect meal conditions. Therefore, this thesis details investigations that assessed muscle protein synthetic responses in both the myofibrillar and sarcoplasmic protein pools under a typical meal setting where a protein-dense food is consumed orally either at rest or after exercise. In study 1, we showed that the postprandial myofibrillar protein synthetic response to protein-dense food ingestion is blunted in overweight and obese compared with normal-weight adults. This finding was related to altered mTORC1 signaling in those groups. In study 2, we demonstrated that basal and postprandial mitochondrial protein synthesis rates are similar in young adults across a wide range of body mass indices. We also showed that muscle inflammatory protein content (e.g. TLR4 and MyD88) increases in response to protein-dense food ingestion in obese, but not normal-weight and overweight young adults. In study 3, we demonstrated that the resistance exercise-induced potentiation of postprandial myofibrillar protein synthesis rates is diminished in obesity young compared with normal-weight adults. However, resistance exercise blunts the obesity-related increase in TLR protein after protein-dense food ingestion. The studies contained in this dissertation show an anabolic resistance to protein-dense food ingestion in obese adults that appears to be limited to the myofibrillar protein sub-fraction of skeletal muscle. Our findings suggest that contractile protein remodeling is a primary impairment in muscles of people with obesity and that exercise strategies to overcome this anabolic resistance are needed
