Skeletal muscle exhibits great plasticity in response to altered activity levels, ultimately resulting in tissue remodelling and substantial changes in mass. Animal research would suggest that the ubiquitin proteasome system, in particular the ubiquitin ligases MAFbx/atrogin-1 and MuRF1, are instrumental to the processes underlying these changes. This review article therefore examines the role of proteasomal-mediated protein degradation in human skeletal muscle in health and disease. Specifically, the effects of exercise, disuse and inflammatory disease states on the ubiquitin proteasome system in human skeletal muscle are examined. The article also identifies several inconsistencies between published human studies and data obtained from animal models of muscle atrophy, highlighting the need for a more comprehensive examination of the molecular events responsible for modulating muscle mass in humans.

Obesity is increasing, yet despite the necessity of maintaining muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 6 1.1 kg $ m 22) and 15 healthy-weight (BMI 23.4 6 0.3 kg $ m 22) older men (55-75 years old) participated in a study that determined muscle protein synthesis (MPS) and leg protein breakdown (LPB) under postabsorptive (hypoinsulinemic-euglycemic clamp) and postprandial (hyperinsulinemic hyperaminoacidemiceuglycemic clamp) conditions. Obesity was associated with systemic inflammation, greater leg fat mass, and patterns of mRNA expression consistent with muscle deconditioning, whereas leg lean mass, strength, and work done during maximal exercise were no different. Under postabsorptive conditions, MPS and LPB were equivalent between groups, whereas insulin and amino acid administration increased MPS in only healthy-weight subjects and was associated with lower leg glucose disposal (LGD) (63%) in obese men. Blunting of MPS in the obese men was offset by an apparent decline in LPB, which was absent in healthy-weight subjects. Lower postprandial LGD in obese subjects and blunting of MPS responses to amino acids suggest that obesity in older adults is associated with diminished muscle metabolic quality. This does not, however, appear to be associated with lower leg lean mass or strength.

The ability to maintain skeletal muscle mass appears to be impaired in insulin resistant conditions. The present study investigated the effect of lipid induced insulin resistance on the rate of muscle protein synthesis. Seven healthy male volunteers (23 ± 1 y, 24 ± 1 kg/m2) underwent a 7 h intravenous infusion of [ring‐2H5]phenylalanine (0.5 mg/kg/h) on two randomised occasions combined with either 0.9% saline or 10% Intralipid (100 mL/h; Fresenius Kabi, Germany). After a 4 h ‘basal’ period, a 21 g bolus of amino acids (except phenylalanine and tyrosine) was administered in a 440 mL solution nasogastrically, and a 3 h euglycaemic (4.5 mmol/L) hyperinsulinemic (50 mU/m2/min) clamp was commenced (‘fed’ period). Muscle biopsies were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion resulted in elevated levels of plasma free fatty acids when compared to saline (P<0.001), which reduced fed glucose disposal by 20% (P<0.01) and pyruvate dehydrogenase complex activation by 50% (P<0.05). Furthermore, whereas mixed muscle fractional synthetic rate increased from the basal to fed period during saline infusion (0.040 ± 0.010 to 0.067 ± 0.013 %/h; P<0.05), it did not respond during lipid infusion (0.048 ± 0.013 to 0.038 ± 0.005 %/h), despite the same circulating insulin and leucine concentrations. Thus, lipid induced insulin resistance results in anabolic resistance to amino acid ingestion in healthy young men.