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Muscle anabolic resistance to dietary protein is associated with obesity and insulin resistance. However, the contribution of excess consumption of fat to anabolic resistance is not well studied. The aim of these studies was to test the hypothesis that acute and short-term dietary fat overload will impair the skeletal muscle protein synthetic response to dietary protein ingestion. Eight overweight/obese males [46.4±1.4 years, BMI 32.3±5.4 kg/m2] participated in the acute feeding study, which consisted of 2 randomised crossover trials. On each occasion, subjects ingested an oral meal (with and without fat emulsion) 4h before the coingestion of milk protein, intrinsically labelled with [1-13C]phenylalanine, and dextrose. Nine overweight/obese males [44.0±1.7 years, BMI 30.1±1.1 kg/m2] participated in the chronic study, which consisted of a baseline 1-week isocaloric diet followed by a 2-week high fat diet (+25% energy excess). Acutely, incorporation of dietary amino acids into the skeletal muscle was 2-fold higher (P<0.05) in the lipid trial compared to control. There was no effect of prior lipid ingestion on indices of insulin sensitivity (muscle glucose uptake, PDC activity and Akt phosphorylation) in response to the protein/dextrose drink. Fat overfeeding had no effect on muscle protein synthesis or glucose disposal in response to whey protein ingestion, despite increased muscle DAG C16:0 (P=0.06) and ceramide C16:0 (P<0.01) levels. Neither acute nor short-term dietary fat overload has a detrimental effect on skeletal muscle protein synthetic response to dietary protein ingestion in overweight/obese men, suggesting dietary-induced accumulation of intramuscular lipids per se is not associated with anabolic resistance.

Animal models of overt statin myopathy reveal clear negative effects on muscle protein and carbohydrate metabolism, which appear to be linked to changes in Akt/FOXO signalling. Forcibly increasing muscle carbohydrate flux under these conditions by pharmacological means blocks statin myopathy. Human volunteer research has delivered less definitive mechanistic insight of the aetiology of statin-related metabolic dysregulation, with little evidence of profound changes in muscle protein and carbohydrate metabolism to date in statin myalgia. However, this may be at least partly explained by statin myalgic patients stopping or changing statin medication before overt muscle pathology has developed to anything like that resembling overt muscle myopathy. Several lines of evidence have associated statin therapy with increased risk of new-onset diabetes and dysregulation of glucose control, but the mechanisms underpinning these observations are currently unresolved.

Aim: Muscle thickness (MT) measured by ultrasound has been used to estimate cross-sectional area (measured by CT and MRI) at a single time-point. We tested whether MT could be used as a valid marker of MRI determined muscle anatomical cross-sectional area (ACSA) and volume changes following resistance training (RT). Methods: Nine healthy, young, male volunteers (24±2 y.o., BMI 24.1±2.8 kg/m2) had vastus lateralis (VL) muscle volume (VOL) and ACSA mid (at 50% of femur length, FL) assessed by MRI, and VL MT measured by ultrasound at 50% FL. Measurements were taken at baseline and after 12 weeks of isokinetic RT. Differences between baseline and post-training were assessed by Student’s paired t-test. The relationships between MRI and ultrasound measurements were tested by Pearson’s correlation. Results: After RT, MT increased by 7.5±6.1% (p<0.001), ACSAmid by 5.2±5% (p<0.001) and VOL by 5.0±6.9% (p<0.05) (values: means±S.D.). Positive correlations were found, at baseline and 12 weeks, between MT and ACSAmid (r=0.82, p<0.001 and r=0.73, p<0.001, respectively), and between MT and VOL (r=0.76, p < 0.001 and r=0.73, p < 0.001, respectively). The % change in MT with training was correlated with % change in ACSAmid (r=0.69, p = 0.01), but not % change in VOL (r= 0.33, p>0.05). Conclusions: These data support evidence that MT is a reliable index of muscle ACSAmid and VOL at a single time-point. MT changes following RT are associated with parallel changes in muscle ACSAmid but not with the changes in VOL, highlighting the impact of RT on regional hypertrophy.

Statins are associated with muscle myalgia and myopathy, which probably reduce habitual physical activity. This is particularly relevant to older people who are less active, sarcopaenic and at increased risk of statin myalgia. We hypothesised that statin myalgia would be allied to impaired strength and work capacity in older people, and determined whether differences aligned with divergences in lean mass, protein turnover, insulin sensitivity and the molecular regulation of these processes. Knee extensor strength and work output during 30 maximal isokinetic contractions were assessed in healthy male volunteers, nine with no statin use (control 70.4 ± 0.7 years) and nine with statin myalgia (71.5 ± 0.9 years). Whole body and leg glucose disposal, muscle myofibrillar protein synthesis (MPS) and leg protein breakdown (LPB) were measured during fasting (≈5 mU l(-1) insulin) and fed (≈40 mU l(-1) insulin + hyperaminoacidaemia) euglyceamic clamps. Muscle biopsies were taken before and after each clamp. Lean mass, MPS, LPB and strength were not different but work output during the initial three isokinetic contractions was 19% lower (P < 0.05) in statin myalgic subjects due to a delay in time to reach peak power output. Statin myalgic subjects had reduced whole body (P = 0.05) and leg (P < 0.01) glucose disposal, greater abdominal adiposity (P < 0.05) and differential expression of 33 muscle mRNAs (5% false discovery rate (FDR)), six of which, linked to mitochondrial dysfunction and apoptosis, increased at 1% FDR. Statin myalgia was associated with impaired muscle function, increased abdominal adiposity, whole body and leg insulin resistance, and evidence of mitochondrial dysfunction and apoptosis.

Obesity is increasing, yet despite the necessity to maintain muscle mass and function with age, the effect of obesity on muscle protein turnover in older adults remains unknown. Eleven obese (BMI 31.9 ±1.1) and 15 healthy weight (HW; BMI 23.4 ±0.3) older men (55-75 years old) participated in a study that determined muscle protein synthesis (MPS) and leg protein breakdown (LPB) under post-absorptive (hypoinsulinaemic euglycaemic clamp) and post-prandial (hyperinsulinemic hyperaminoacidaemic euglycaemic clamp) conditions. Obesity was associated with systemic inflammation, greater leg fat mass, and patterns of mRNA expression consistent with muscle deconditioning, whilst leg lean mass, strength and work done during maximal exercise were no different. Under post-absorptive conditions, MPS and LPB were equivalent between groups, while insulin and amino acid administration increased MPS in only HW subjects and was associated with lower leg glucose disposal (LGD, 63%) in obese. Blunting of MPS in the obese was offset by an apparent decline in LPB, which was absent in HW subjects. Lower post-prandial LGD in obese subjects and blunting of MPS responses to amino acids suggests obesity in older adults is associated with diminished muscle metabolic quality. However this doesn’t appear to be associated with lower leg lean mass or strength.