No abstract

Obesity is often associated with insulin resistance and mitochondrial dysfunction within skeletal muscles, but the causative factors are not clearly identified. The present study examined the role of nutrition, both qualitatively and quantitatively, in the induction of muscle mitochondrial defects. Two experimental diets [high sucrose (SU) and high fat (F)] were provided for 6 wk to male Wistar rats at 2 levels of energy [standard (N) and high (H)] and compared with a standard energy cornstarch-based diet (C). Insulin sensitivity (intraperitoneal glucose tolerance test, IPGTT) and intramyocellular triglyceride (IMTG) content (1H MRS) were determined at wk 5. Mitochondrial oxidative phosphorylation and superoxide anion radical (MSR) production were assessed on soleus (oxidative) and tibialis (glycolytic) muscles. Experimental diets induced hyperinsulinemia during IPGTT (P < 0.01 vs. C). Rats in the HSU and HF groups were hyperglycemic relative to the C group, P < 0.05 vs. C. The severity of insulin resistance paralleled IMTG accumulation (P < 0.05). In soleus, mitochondrial respiration and ATP production rates were lower in HSU and HF than in C (P < 0.05). By contrast, respiration was unaffected by the diets in tibialis, whereas ATP production tended to be lower in rats fed the experimental diets compared with C (P = 0.09). Mitochondrial adaptations were associated with more than a 50% reduction in MSR production in HSU and HF compared with C in both soleus (P < 0.05) and tibialis (P < 0.01). Changes in mitochondrial functions in the NSU and NF groups were intermediate and not significantly different from C. Therefore, excess fat or sucrose and more importantly, excess energy intake by rats is associated with muscle type-specific mitochondrial adaptations, which contribute to decrease mitochondrial production of ATP and reactive oxygen species.

Caloric restriction (CR) delays the onset of age-related mitochondrial abnormalities but does not prevent the decline in ATP production needed to sustain muscle protein fractional synthesis rate (FSR) and contractile activity. We hypothesized that improving mitochondrial activity and FSR using a CR diet with maintained protein intakes could enhance myofibrillar protein FSR and consequently improve muscle strength in aging rats. Wistar rats (21 months old) were fed either an ad libitum (AL), 40% protein-energy restricted (PER) or 40% AL-isonitrogenous energy restricted (ER) diet for 5 months. ATP production, electron transport chain activity, reactive oxygen species (ROS) generation, protein carbonyl content and FSR were determined in both tibialis anterior (TA) and soleus muscle mitochondria. Myosin and actin FSR and grip force were also investigated. The ER diet led to improved mitochondrial activity and ATP production in the TA and soleus muscles in comparison with PER. Furthermore, mitochondrial FSR in the TA was enhanced under the ER diet but diminished under the PER. Mitochondrial protein carbonyl content was decreased by both the ER and PER diets. The ER diet was able to improve myosin and actin FSR and grip force. Therefore, the synergistic effects of CR with maintained protein intake may help to limit the progression of sarcopenia by optimizing the turnover rates and functions of major proteins in skeletal muscle.

OBJECTIVE:To test the hypothesis that the increase in fat mass observed with aging might be related to a decrease in wholebody fat oxidation. SUBJECTS AND MEASUREMENTS: Forty volunteers had measurements of sleeping and 24 h substrate oxidation in calorimetric chambers, body composition with the 18 O dilution technique, VO 2max , and ®ber composition analysis from a biopsy of vastus lateralis. They were divided into 10 young women, 10 young men, 10 elderly women and 10 elderly men. RESULTS: Sleeping fat oxidation and 24 h fat oxidation were lower in women than in men and in elderly than in young participants. Sleeping fat oxidation was correlated to fat-free mass and energy balance (multivariate analysis). Twenty four hour fat oxidation was correlated to total energy expenditure and energy balance (multivariate analysis). After adjustment for differences in these factors, sleeping and 24 h fat oxidation were no longer different between age and sex groups. None of the parameters of macronutrient metabolism was correlated with muscle ®ber composition. CONCLUSION: Our data suggest that fat oxidation is lower in elderly subjects. This difference could favour fat mass gain if fat intake is not adequately reduced. Differences in fat-free mass and in total energy expenditure appear to participate in the reduction in fat oxidation.

OBJECTIVE: To address whether: (1) bioelectrical impedance analysis (BIA) can provide precise and accurate estimates of total body water (TBW) and extracellular water (ECW) in healthy elderly subjects, that display ageinduced changes in body composition, (2) BIA models are improved by introducing variables related to geometrical body-shape and osmolarity. DESIGN: Cross-validation of available BIA models and models developed in the study. SUBJECTS: 58 healthy elderly subjects (31 women, 27 men, 66.8 AE 4.7 y, mean AE s.d.) MEASUREMENTS: BIA at 5, 50 and 100 kHz, 18 O labelled water measurements of TBW, Br measurements of ECW, anthropometric variables, plasma osmolarity. RESULTS: Published BIA models for estimating TBW, entail various degrees of bias. Precise models (SEE of the models 0.8 L at 100 kHz, 1.0 L at 50 kHz) involving height 2 aresistance, weight, gender, circumferences and plasma osmolarity were established with data from 30 subjects chosen at random. Cross-validation of an independent group (n 28) showed no bias (71.5 AE 3.2 L at 100 kHz, 71.4 AE 3.2 L at 50 kHz, P NS). CONCLUSION: We conclude that BIA models with increased accuracy and precision for predicting ECW and TBW can be derived in healthy elderly subjects. Repeated measures had a mean difference of 0.2 AE 1.2 L.