Obesity is associated with altered muscle protein synthetic and breakdown responses to increased nutrient delivery in older adult humans, but not reduced muscle mass or contractile function

Obesity – A Physiological Perspective (Newcastle, UK) (2014) Proc Physiol Soc 32, PC025

Poster Communications: Obesity is associated with altered muscle protein synthetic and breakdown responses to increased nutrient delivery in older adult humans, but not reduced muscle mass or contractile function

A. Murton1,3, K. Marimuthu1,3, J. E. Mallinson1,3, A. L. Selby2,3, K. Smith2,3, M. J. Rennie2,3, P. L. Greenhaff1,3

1. School of Biomedical Sciences, The University of Nottingham, Nottingham, United Kingdom. 2. School of Graduate Entry Medicine & Health, The University of Nottingham, Derby, United Kingdom. 3. MRC/ARUK Centre for Musculoskeletal Ageing Research, The University of Nottingham, Nottingham, United Kingdom.

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The incidence of obesity is increasing among older adults (Fakhouri et al., 2012), yet despite the central need to maintain muscle mass and function to preserve quality of life, the effect of obesity on muscle protein turnover in this population remains unknown. To investigate this, 11 obese (age: 66.4 ±1.8; BMI: 31.9 ±1.1] and 15 lean [age: 66.7 ±1.1; BMI: 23.4 ±0.3] male subjects underwent assessment of muscle protein synthesis (MPS) and leg protein breakdown (LPB) under hypoinsulinemic (5 mU.l-1; post-absorptive) and hyperinsulinemic (40 mU.l-1; post-prandial) euglycaemic (4.5 mmol.l-1) clamp conditions, the latter administered in conjunction with mixed-amino acids (10 g.h-1). Leg fat and lean mass were assessed by dual-energy x-ray absorptiometry, along with quadriceps isometric strength of the dominant leg. Statistical differences in anthropometric measures and leg glucose disposal rate were determined using unpaired Student’s t-test. Differences in MPS and LPB were determined by 2-way ANOVA; when a significant effect was observed a Student’s t-test with Šidák correction was performed to located differences. Significance was accepted when P<0.05 and values reported as mean ±SEM. Obesity was associated with a significant increase in leg fat mass (lean: 5.7 ±0.5 kg; obese: 9.4 ±0.6 kg; P<0.001), whilst leg lean mass (lean: 9.6 ±0.4 kg; obese: 10.1 ±0.4 kg) and quadriceps strength (lean: 34.3 ± 2.5 kg; obese: 33.9 ± 3.0 kg) were unaffected. Under post-absorptive conditions, MPS and LPB were not different between groups. Insulin and amino acid administration significantly increased muscle fractional synthetic rate of myofibrillar proteins in lean (0.047 ±0.004 to 0.099 ±0.011 %.h-1; P<0.001) but not obese subjects (0.045 ±0.004 to 0.062 ±0.006 %.h-1; n.s.), but this blunting of MPS was offset by a parallel decline in LPB in the obese (48.5 ±9.5 to 29.9 ±5.5 nmol.min-1.100g leg mass-1; P<0.05) but not lean (49.8 ±8.5 to 44.7 ±7.2 nmol.min-1.100g leg mass-1; n.s.) individuals. Obesity also resulted in a 63% reduction in leg glucose disposal rate under steady state conditions in the post-prandial state (P<0.001). Thus, obesity in the older adult is associated with a decline in muscle metabolic quality, evidenced by reduced glucose disposal and blunting of the protein synthetic response to amino acids, but this does not lead to a decline in muscle mass in part due to a reciprocal decrease in LPB rates.



Where applicable, experiments conform with Society ethical requirements.

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