Protein turnover modifications induced by the protein feeding pattern still persist after the end of the diets

This study was undertaken to determine whether the protein feeding pattern could induce chronic adaptation of protein turnover. After a 15-day adaptive period, elderly (68 yr) and young (26 yr) women received, for 14 days, a diet providing 200 KJ x kg fat-free mass (FFM)(-1) x day(-1), where the daily protein intake (1.7 g protein x kg FFM(-1) x day(-1)) was either spread over 4 meals in the spread pattern or mainly (80%) consumed at noon in the pulse pattern. One day after the end of the dietary treatment, whole body leucine kinetics were measured by use of a continuous [(13)C]leucine infusion, both in the postabsorptive state and in the same fed state. The pulse pattern was able to induce, in young as in elderly women, a lower postabsorptive leucine oxidation and endogenous leucine flux than the spread pattern and improved the responsiveness of nonoxidative leucine disposal during 4-h oral feeding. Thus the pulse pattern was able to induce chronic regulation of protein metabolism in young as in elderly women.     

Whole body leucine flux in HIV-infected patients treated with or without protease inhibitors

The present study was carried out to assess the effects of protease inhibitor (PI) therapy on basal whole body protein metabolism and its response to acute amino acid-glucose infusion in 14 human immunodeficiency virus (HIV)-infected patients. Patients treated with PIs (PI+, 7 patients) or without PIs (PI-, 7 patients) were studied after an overnight fast during a 180-min basal period followed by a 140-min period of amino acid-glucose infusion. Protein metabolism was investigated by a primed constant infusion of l-[1-(13)C]leucine. Dual-energy X-ray absorptiometry for determination of fat-free mass (FFM) and body fat mass measured body composition. In the postabsorptive state, whole body leucine balance was 2.5 times (P < 0.05) less negative in the PI+ than in the PI- group. In HIV-infected patients treated with PIs, the oxidative leucine disposal during an acute amino acid-glucose infusion was lower (0.58 +/- 0.09 vs. 0.81 +/- 0.07 micromol x kg FFM(-1) x min(-1) using plasma [(13)C]leucine enrichment, P = 0.06; or 0.70 +/- 0.10 vs. 0.99 +/- 0.08 micromol x kg FFM(-1) x min(-1) using plasma [(13)C]ketoisocaproic acid enrichment, P = 0.04 in PI+ and PI- groups, respectively) than in patients treated without PIs. Consequently, whole body nonoxidative leucine disposal (an index of protein synthesis) and leucine balance (0.50 +/- 0.10 vs. 0.18 +/- 0.06 micromol x kg FFM x (-1) x min(-1) in PI+ and PI- groups respectively, P < 0.05) were significantly improved during amino acid-glucose infusion in patients treated with PIs. However, whereas the response of whole body protein anabolism to an amino acid-glucose infusion was increased in HIV-infected patients treated with PIs, any improvement in lean body mass was detected.     

Collagen synthesis in human musculoskeletal tissues and skin

We have developed a direct method for the measurement of human musculoskeletal collagen synthesis on the basis of the incorporation of stable isotope-labeled proline or leucine into protein and have used it to measure the rate of synthesis of collagen in tendon, ligament, muscle, and skin. In postabsorptive, healthy young men (28 +/- 6 yr) synthetic rates for tendon, ligament, muscle, and skin collagen were 0.046 +/- 0.005, 0.040 +/- 0.006, 0.016 +/- 0.002, and 0.037 +/- 0.003%/h, respectively (means +/- SD). In postabsorptive, healthy elderly men (70 +/- 6 yr) the rate of skeletal muscle collagen synthesis is greater than in the young (0.023 +/- 0.002%/h, P < 0.05 vs. young). The rates of synthesis of tendon and ligament collagen are similar to those of mixed skeletal muscle protein in the postabsorptive state, whereas the rate for muscle collagen synthesis is much lower in both young and elderly men. After nutrient provision, collagen synthesis was unaltered in tendon and skeletal muscle, remaining at postabsorptive values (young: tendon, 0.045 +/- 0.008%/h; muscle, 0.016 +/- 0.003%/h; elderly: muscle, 0.024 +/- 0.003%/h). These results demonstrate that the rate of human musculoskeletal tissue collagen synthesis can be directly and robustly measured using stable isotope methodology.     

The nature of the ingested protein has no effect on lean body mass during energy restriction in overweight rats

Severe energy restriction in obesity not only leads to fat mass loss but also to lean mass loss. The aim of this study was to compare the capacity of casein, a slowly digested protein, and milk soluble proteins (MSP; rapidly digested) to limit the loss of lean mass induced by energy restriction. Obesity was first induced in male Wistar rats by a 5-week feeding with a high-fat high-sucrose diet. The impact of energy restriction was then studied with high-protein (32%) diets containing either casein, MSP, or a 50/50 mixture of both proteins for 3 weeks (n = 10 per group). Food intake, body weight, nitrogen balance, creatinine, and 3-methyl-histidine excretion were measured during energy restriction. Then, tissue weights, plasma metabolic parameters (amino acids, glucose, insulin, cholesterol, triglycerides), and in vivo liver and extensor digitorum longus (EDL) muscle protein synthesis rates were measured in postabsorptive state at the end of the experimental period. Although significant differences relevant to protein metabolism were observed between groups (protein intake, plasma amino acid concentrations, fecal nitrogen excretion, muscle protein synthesis rates), week per week, there were no significant differences in nitrogen balance whatever the protein used. In conclusion, our results show that in young overweight energy restricted rats, using a high-protein diet, the nature of protein intake has no influence on body protein retention.     

Hyperglycemia compensates for diet-induced insulin resistance in liver and skeletal muscle of rats

High-fat and high-sucrose diets increase the contribution of gluconeogenesis to glucose appearance (glc R(a)) under basal conditions. They also reduce insulin suppression of glc R(a) and insulin-stimulated muscle glycogen synthesis under euglycemic, hyperinsulinemic conditions. The purpose of the present study was to determine whether these impairments influence liver and muscle glycogen synthesis under hyperglycemic, hyperinsulinemic conditions. Male rats were fed a high-sucrose, high-fat, or low-fat, starch control diet for either 1 (n = 5-7/group) or 5 wk (n = 5-6/group). Studies involved two 90-min periods. During the first, a basal period (BP), [6-3H]glucose was infused. In the second, a hyperglycemic period (HP), [6-3H]glucose, [6-14C]glucose, and unlabeled glucose were infused. Plasma glucose (BP: 111.2 +/- 1.5 mg/dl; HP: 172.3 +/- 1.5 mg/dl), insulin (BP: 2.5 +/- 0.2 ng/ml; HP: 4.9 +/- 0.3 ng/ml), and glucagon (BP: 81.8 +/- 1.6 ng/l; HP: 74.0 +/- 1.3 ng/l) concentrations were not significantly different among diet groups or with respect to time on diet. There were no significant differences among groups in the glucose infusion rate (mg x kg(-1) x min(-1)) necessary to maintain arterial glucose concentrations at approximately 170 mg/dl (pooled average: 6.4 +/- 0.8 at 1 wk; 6.4 +/- 0.7 at 5 wk), percent suppression of glc R(a) (44.4 +/- 7.8% at 1 wk; 63.2 +/- 4.3% at 5 wk), tracer-estimated net liver glycogen synthesis (7.8 +/- 1.3 microg x g liver(-1) x min(-1) at 1 wk; 10.5 +/- 2.2 microg x g liver(-1) x min(-1) at 5 wk), indirect pathway glycogen synthesis (3.7 +/- 0.9 microg x g liver(-1) x min(-1) at 1 wk; 3.4 +/- 0.9 microg x g liver(-1) x min(-1) at 5 wk), or tracer-estimated net muscle glycogenesis (1.0 +/- 0.3 microg x g muscle(-1) x min(-1) at 1 wk; 1.6 +/- 0.3 microg x g muscle(-1) x min(-1) at 5 wk). These data suggest that hyperglycemia compensates for diet-induced insulin resistance in both liver and skeletal muscle.     

Measurement of human mixed muscle protein fractional synthesis rate depends on the choice of amino acid tracer

The goal of this study was to discover whether using different tracers affects the measured rate of muscle protein synthesis in human muscle. We therefore measured the mixed muscle protein fractional synthesis rate (FSR) in the quadriceps of older adults during basal, postabsorptive conditions and mixed meal feeding (70 mg protein x kg fat-free mass(-1) x h(-1) x 2.5 h) by simultaneous intravenous infusions of [5,5,5-(2)H(3)]leucine and either [ring-(13)C(6)]phenylalanine or [ring-(2)H(5)]phenylalanine and analysis of muscle tissue samples by gas chromatography-mass spectrometry. Both the basal FSR and the FSR during feeding were approximately 20% greater (P < 0.001) when calculated from the leucine labeling in muscle tissue fluid and proteins (fasted: 0.063 +/- 0.005%/h; fed: 0.080 +/- 0.007%/h) than when calculated from the phenylalanine enrichment data (0.051 +/- 0.004 and 0.066 +/- 0.005%/h, respectively). The feeding-induced increase in the FSR ( approximately 20%; P = 0.011) was not different with leucine and phenylalanine tracers (P = 0.69). Furthermore, the difference between the leucine- and phenylalanine-derived FSRs was independent of the phenylalanine isotopomer used (P = 0.92). We conclude that when using stable isotope-labeled tracers and the classic precursor product model to measure the rate of muscle protein synthesis, absolute rates of muscle protein FSR differ significantly depending on the tracer amino acid used; however, the anabolic response to feeding is independent of the tracer used. Thus different precursor amino acid tracers cannot be used interchangeably for the evaluation of muscle protein synthesis, and data from studies using different tracer amino acids can be compared qualitatively but not quantitatively.     

Regular Multicomponent Exercise Increases Physical Fitness and Muscle Protein Anabolism in Frail,Obese, Older Adults

Aging is associated with a decline in strength, endurance, balance, and mobility. Obesity worsens the age‐related impairment in physical function and often leads to frailty. The American College of Sports Medicine recommends a multicomponent (strength, endurance, flexibility, and balance) exercise program to maintain physical fitness. However, the effect of such an exercise program on physical fitness in frail, obese older adults is not known. We therefore determined the effect of a 3‐month long multicomponent exercise training program, on endurance (peak aerobic capacity (VO₂ peak)), muscle strength, muscle mass, and the rate of muscle protein synthesis (basal rate and anabolic response to feeding) in nine 65‐ to 80‐year‐old, moderately frail, obese older adults. After 3 months of training, fat mass decreased (P < 0.05) whereas fat‐free mass (FFM), appendicular lean body mass, strength, and VO₂ peak increased (all P < 0.05). Regular strength and endurance exercise increased the mixed muscle protein fractional synthesis rate (FSR) but had no effect on the feeding‐induced increase in muscle protein FSR (～0.02%/h increase from basal values both before and after exercise training; effect of feeding: P = 0.02; effect of training: P = 0.047; no interaction: P = 0.84). We conclude that: (i) a multicomponent exercise training program has beneficial effects on muscle mass and physical function and should therefore be recommended to frail, obese older adults, and (ii) regular multicomponent exercise increases the basal rate of muscle protein synthesis without affecting the magnitude of the muscle protein anabolic response to feeding.     

Evaluation of protein requirements for trained strength athletes.

Leucine kinetic and nitrogen balance (NBAL) methods were used to determine the dietary protein requirements of strength athletes (SA) compared with sedentary subjects (S). Individual subjects were randomly assigned to one of three protein intakes: low protein (LP) = 0.86 g protein.kg-1.day-1, moderate protein (MP) = 1.40 g protein.kg-1.day-1, or high protein (HP) = 2.40 g protein.kg-1.day-1 for 13 days for each dietary treatment. NBAL was measured and whole body protein synthesis (WBPS) and leucine oxidation were determined from L-[1-13C]leucine turnover. NBAL data were used to determine that the protein intake for zero NBAL for S was 0.69 g.kg-1.day-1 and for SA was 1.41 g.kg-1.day-1. A suggested recommended intake for S was 0.89 g.kg-1.day-1 and for SA was 1.76 g.kg-1.day-1. For SA, the LP diet did not provide adequate protein and resulted in an accommodated state (decreased WBPS vs. MP and HP), and the MP diet resulted in a state of adaptation [increase in WBPS (vs. LP) and no change in leucine oxidation (vs. LP)]. The HP diet did not result in increased WBPS compared with the MP diet, but leucine oxidation did increase significantly, indicating a nutrient overload. For S the LP diet provided adequate protein, and increasing protein intake did not increase WBPS. On the HP diet leucine oxidation increased for S. These results indicated that the MP and HP diets were nutrient overloads for S. There were no effects of varying protein intake on indexes of lean body mass (creatinine excretion, body density) for either group. In summary, protein requirements for athletes performing strength training are greater than for sedentary individuals and are above current Canadian and US recommended daily protein intake requirements for young healthy males.     

Resistance Training Preserves Fat‐free Mass Without Impacting Changes in Protein Metabolism After Weight Loss in Older Women

This study assessed the effects of resistance training (RT) on energy restriction–induced changes in body composition, protein metabolism, and the fractional synthesis rate of mixed muscle proteins (FSRm) in postmenopausal, overweight women. Sixteen women (age 68 ± 1 years, BMI 29 ± 1 kg/m², mean ± s.e.m.) completed a 16‐week controlled diet study. Each woman consumed 1.0 g protein/kg/day. At baseline (weeks B1–B3) and poststudy (weeks RT12–RT13), energy intake matched each subject's need and during weeks RT1–RT11 was hypoenergetic by 2,092 kJ/day (500 kcal/day). From weeks RT1 to RT13, eight women performed RT 3 day/week (RT group) and eight women remained sedentary (SED group). RT did not influence the energy restriction–induced decrease in body mass (SED ?5.8 ± 0.6 kg; RT ?5.0 ± 0.2 kg) and fat mass (SED ?4.1 ± 0.9 kg; RT ?4.7 ± 0.5 kg). Fat free mass (FFM) and total body water decreased in SED (?1.6 ± 0.4 and ?2.1 ± 0.5 kg) and were unchanged in RT (?0.3 ± 0.4 and ?0.4 ± 0.7 kg) (group‐by‐time, P ≤ 0.05 and P = 0.07, respectively). Protein–mineral mass did not change in either group (SED 0.4 ± 0.2 kg; RT 0.1 ± 0.4 kg). Nitrogen balance, positive at baseline (2.2 ± 0.3 g N/day), was unchanged poststudy. After body mass loss, postabsorptive (PA) and postprandial (PP) leucine turnover, synthesis, and breakdown decreased. Leucine oxidation and balance were not changed. PA and total (PA + PP) FSRm in the vastus lateralis were higher after weight loss. RT did not influence these protein metabolism responses. In summary, RT helps older women preserve FFM during body mass loss. The comparable whole‐body nitrogen retentions, leucine kinetics, and FSRm between groups are consistent with the lack of differential protein–mineral mass change.     

Protein coingestion stimulates muscle protein synthesis during resistance-type exercise

In contrast to the effect of nutritional intervention on postexercise muscle protein synthesis, little is known about the potential to modulate protein synthesis during exercise. This study investigates the effect of protein coingestion with carbohydrate on muscle protein synthesis during resistance-type exercise. Ten healthy males were studied in the evening after they consumed a standardized diet throughout the day. Subjects participated in two experiments in which they ingested either carbohydrate or carbohydrate with protein during a 2-h resistance exercise session. Subjects received a bolus of test drink before and every 15 min during exercise, providing 0.15 g x kg(-1) x h(-1) carbohydrate with (CHO + PRO) or without (CHO) 0.15 g x kg(-1) x h(-1) protein hydrolysate. Continuous intravenous infusions with l-[ring-(13)C(6)]phenylalanine and l-[ring-(2)H(2)]tyrosine were applied, and blood and muscle biopsies were collected to assess whole body and muscle protein synthesis rates during exercise. Protein coingestion lowered whole body protein breakdown rates by 8.4 +/- 3.6% (P = 0.066), compared with the ingestion of carbohydrate only, and augmented protein oxidation and synthesis rates by 77 +/- 17 and 33 +/- 3%, respectively (P < 0.01). As a consequence, whole body net protein balance was negative in CHO, whereas a positive net balance was achieved after the CHO + PRO treatment (-4.4 +/- 0.3 vs. 16.3 +/- 0.4 micromol phenylalanine x kg(-1) x h(-1), respectively; P < 0.01). In accordance, mixed muscle protein fractional synthetic rate was 49 +/- 22% higher after protein coingestion (0.088 +/- 0.012 and 0.060 +/- 0.004%/h in CHO + PRO vs. CHO treatment, respectively; P < 0.05). We conclude that, even in a fed state, protein coingestion stimulates whole body and muscle protein synthesis rates during resistance-type exercise.     

Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability

Insulin promotes muscle anabolism, but it is still unclear whether it stimulates muscle protein synthesis in humans. We hypothesized that insulin can increase muscle protein synthesis only if it increases muscle amino acid availability. We measured muscle protein and amino acid metabolism using stable-isotope methodologies in 19 young healthy subjects at baseline and during insulin infusion in one leg at low (LD, 0.05), intermediate (ID, 0.15), or high (HD, 0.30 mUxmin(-1)x100 ml(-1)) doses. Insulin was infused locally to induce muscle hyperinsulinemia within the physiological range while minimizing the systemic effects. Protein and amino acid kinetics across the leg were assessed using stable isotopes and muscle biopsies. The LD did not affect phenylalanine delivery to the muscle (-9 +/- 18% change over baseline), muscle protein synthesis (16 +/- 26%), breakdown, or net balance. The ID increased (P < 0.05) phenylalanine delivery (+63 +/- 38%), muscle protein synthesis (+157 +/- 54%), and net protein balance, with no change in breakdown. The HD did not change phenylalanine delivery (+12 +/- 11%) or muscle protein synthesis (+9 +/- 19%), and reduced muscle protein breakdown (-17 +/- 15%), thus improving net muscle protein balance but to a lesser degree than the ID. Changes in muscle protein synthesis were strongly associated with changes in muscle blood flow and phenylalanine delivery and availability. In conclusion, physiological hyperinsulinemia promotes muscle protein synthesis as long as it concomitantly increases muscle blood flow, amino acid delivery and availability.     

Age-related differences in muscle power during single-step balance recovery

The purpose of this study was to investigate age-related differences in muscle power during a surrogate task of trip recovery. Participants included 10 healthy young men (19-23 years old) and 10 healthy older men (65-83). The task involved releasing participants from a forward-leaning posture. After release, participants attempted to recover their balance using a single step of the right foot. Muscle power at the hip, knee, and ankle of the stepping limb were determined from the product of joint angular velocity and joint torque. Muscle powers during balance recovery followed a relatively consistent pattern in both young and older men, and showed effects of both lean and age. Interestingly, the effects of age did not always involve smaller peak power values in the older men as expected from the well-documented loss of muscle power with aging. Older men exhibited smaller peak muscle power at the knee and larger peak muscle power at the ankle and hip compared to young men. The increases in muscle power at the ankle and hip may result from a neuromuscular adaptation aimed at improving balance recovery ability by compensating for the age-related loss of muscle function.     

The Grey Mouse Lemur Uses Season-Dependent Fat or Protein Sparing Strategies to Face Chronic Food Restriction

During moderate calorie restriction (CR) the heterotherm Microcebus murinus is able to maintain a stable energy balance whatever the season, even if only wintering animals enter into torpor. To understand its energy saving strategies to respond to food shortages, we assessed protein and energy metabolisms associated with wintering torpor expression or summering torpor avoidance. We investigated body composition, whole body protein turnover, and daily energy expenditure (DEE), during a graded (40 and 80%) 35-day CR in short-days (winter; SD40 and SD80, respectively) and long-days (summer; LD40 and LD80, respectively) acclimated animals. LD40 animals showed no change in fat mass (FM) but a 12% fat free mass (FFM) reduction. Protein balance being positive after CR, the FFM loss was early and rapid. The 25% DEE reduction, in LD40 group was mainly explained by FFM changes. LD80 animals showed a steady body mass loss and were excluded from the CR trial at day 22, reaching a survival-threatened body mass. No data were available for this group. SD40 animals significantly decreased their FM level by 21%, but maintained FFM. Protein sparing was achieved through a 35 and 39% decrease in protein synthesis and catabolism (protein turnover), respectively, overall maintaining nitrogen balance. The 21% reduction in energy requirement was explained by the 30% nitrogen flux drop but also by torpor as DEE FFM-adjusted remained 13% lower compared to ad-libitum. SD80 animals were unable to maintain energy and nitrogen balances, losing both FM and FFM. Thus summering mouse lemurs equilibrate energy balance by a rapid loss of active metabolic mass without using torpor, whereas wintering animals spare protein and energy through increased torpor expression. Both strategies have direct fitness implication: 1) to maintain activities at a lower body size during the mating season and 2) to preserve an optimal wintering muscle mass and function.     

Light aerobic physical exercise in combination with leucine and/or glutamine-rich diet can improve the body composition and muscle protein metabolism in young tumor-bearing rats

Nutritional supplementation with some amino acids may influence host??s responses and also certain mechanism involved in tumor progression. It is known that exercise influences body weight and muscle composition. Previous findings from our group have shown that leucine has beneficial effects on protein composition in cachectic rat model as the Walker 256 tumor. The main purpose of this study was to analyze the effects of light exercise and leucine and/or glutamine-rich diet in body composition and skeletal muscle protein synthesis and degradation in young tumor-bearing rats. Walker tumor-bearing rats were subjected to light aerobic exercise (swimming 30?min/day) and fed a leucine-rich (3%) and/or glutamine-rich (4%) diet for 10?days and compared to healthy young rats. The carcasses were analyzed as total water and fat body content and lean body mass. The gastrocnemious muscles were isolated and used for determination of total protein synthesis and degradation. The chemical body composition changed with tumor growth, increasing body water and reducing body fat content and total body nitrogen. After tumor growth, the muscle protein metabolism was impaired, showing that the muscle protein synthesis was also reduced and the protein degradation process was increased in the gastrocnemius muscle of exercised rats. Although short-term exercise (10?days) alone did not produce beneficial effects that would reduce tumor damage, host protein metabolism was improved when exercise was combined with a leucine-rich diet. Only total carcass nitrogen and protein were recovered by a glutamine-rich diet. Exercise, in combination with an amino acid-rich diet, in particular, leucine, had effects beyond reducing tumoral weight such as improving protein turnover and carcass nitrogen content in the tumor-bearing host.     

Whole body and skeletal muscle glutamine metabolism in healthy subjects

We measured glutamine kinetics using L-[5-15N]glutamine and L-[ring-2H5]phenylalanine infusions in healthy subjects in the postabsorptive state and during ingestion of an amino acid mixture that included glutamine, alone or with additional glucose. Ingestion of the amino acid mixture increased arterial glutamine concentrations by approximately 20% (not by 30%; P < 0.05), irrespective of the presence or absence of glucose. Muscle free glutamine concentrations remained unchanged during ingestion of amino acids alone but decreased from 21.0 +/- 1.0 to 16.4 +/- 1.6 mmol/l (P < 0.05) during simultaneous ingestion of glucose due to a decrease in intramuscular release from protein breakdown and glutamine synthesis (0.82 +/- 0.10 vs. 0.59 +/- 0.06 micromol x 100 ml leg(-1) x min(-1); P < 0.05). In both protocols, muscle glutamine inward and outward transport and muscle glutamine utilization for protein synthesis increased during amino acid ingestion; leg glutamine net balance remained unchanged. In summary, ingestion of an amino acid mixture that includes glutamine increases glutamine availability and uptake by skeletal muscle in healthy subjects without causing an increase in the intramuscular free glutamine pool. Simultaneous ingestion of glucose diminishes the intramuscular glutamine concentration despite increased glutamine availability in the blood due to decreased glutamine production.     

Effect of weight loss on the rate of muscle protein synthesis during fasted and fed conditions in obese older adults

Although weight loss ameliorates many of the metabolic abnormalities associated with obesity, there has been reluctance to prescribe weight loss in obese, older individuals because of the fear that it will cause debilitating loss of muscle mass and impair physical function. To gain insight into the mechanisms responsible for the weight loss-induced changes in muscle mass, we measured the rate of muscle protein synthesis (by using stable isotope labeled tracer methodology) during basal, postabsorptive conditions and during mixed meal ingestion in eight obese, older adults: (i) before weight loss therapy, (ii) ~3 months after starting the weight loss intervention (i.e., during the active weight loss phase), when subjects had lost ~7% of their initial body weight, and (iii) after they had lost ~10% of their body weight and maintained this new body weight for ~6 months (~12 months after starting the weight loss intervention). The basal muscle protein fractional synthesis rate (FSR) was not affected by weight loss. Mixed meal ingestion stimulated the rate of muscle protein synthesis, and the anabolic response (i.e., increase in the protein synthesis rate above basal values) was greater (P < 0.05) during negative energy balance and active weight loss at 3 months (0.033 ± 0.012%·per hour, mean ± s.e.m.) than during weight maintenance before and at 12 months of weight loss therapy (0.003 ± 0.003 and 0.008 ± 0.012%·per hour, respectively). We conclude that during dietary calorie restriction and weight loss in older adults, the rate of muscle protein synthesis is not impaired. Thus, the loss of muscle mass must be mediated predominately by adverse effects of dietary calorie restriction on muscle proteolysis.     

Hyperpalatable Diet and Physical Exercise Modulate the Expression of the Glial Monocarboxylate Transporters MCT1 and 4

Hyperpalatable diets (HP) impair brain metabolism, and regular physical exercise has an apparent opposite effect. Here, we combined a prior long-term exposure to HP diet followed by physical exercise and evaluated the impact on some neuroenergetic components and on cognitive performance. We assessed the extracellular lactate concentration, expression of monocarboxylate transporters (MCTs), pyruvate dehydrogenase (PDH), and mitochondrial function in the hippocampus. Male C57BL/6J mice were fed 4 months with HP or a control diet. Subsequently, they were divided in the following groups: control diet sedentary (CDS), control diet exercise (CDE), HP diet sedentary (HPS), and HP diet exercise (HPE) (n = 15 per group) and were engaged for an additional 30-day period of voluntary exercise and HP diet. Relative to the control situation, exercise increased MCT1, MCT4, and PDH protein levels, while the HP diet increased MCT1 and MCT4 protein levels. The production of hydrogen peroxide (H₂O₂) and the mitochondrial membrane potential (??_m) stimulated by succinate in hippocampal homogenates were not significantly different between groups. ADP phosphorylation and the maximal respiratory rate induced by FCCP showed similar responses between groups, implying a normal mitochondrial function. Also, extracellular brain lactate levels were increased in the HPE group compared to other groups soon after performing the Y-maze task. However, such enhanced lactate levels were not associated with improved memory performance. In summary, hippocampal protein expression levels of MCT1 and 4 were increased by physical exercise and HP diet, whereas PDH was only increased by exercise. These observations indicate that a hippocampal metabolic reprogramming takes place in response to these environmental factors.     

Effects of high-fat overfeeding on mitochondrial function, glucose and fat metabolism, and adipokine levels in low-birth-weight subjects

Low birth weight (LBW) is associated with an increased risk of insulin resistance and downregulation of oxidative phosphorylation (OXPHOS) genes when exposed to a metabolic challenge of high-fat overfeeding (HFO). To elaborate further on the differential effects of HFO in LBW subjects, we measured in vivo mitochondrial function, insulin secretion, hepatic glucose production, and plasma levels of key regulatory hormones before and after 5 days of HFO in 20 young LBW and 26 normal-birth-weight (NBW) men. The LBW subjects developed peripheral insulin resistance after HFO due to impaired endogenous glucose storage (9.42 ± 4.19 vs. 5.91 ± 4.42 mg·kg FFM(-1)·min(-1), P = 0.01). Resting muscle phosphorcreatine and total ATP in muscle increased significantly after HFO in LBW subjects only, whereas additional measurements of mitochondrial function remained unaffected. Despite similar plasma FFA levels, LBW subjects displayed increased fat oxidation during insulin infusion compared with normal-birth-weight (NBW) subjects after HFO (0.37 ± 0.35 vs. 0.17 ± 0.33 mg·kg FFM(-1)·min(-1), P = 0.02). In contrast to NBW subjects, the plasma leptin levels of LBW subjects did not increase, and the plasma gastric inhibitory polypeptide (GIP) as well as pancreatic polypeptide (PP) levels increased less in LBW compared with NBW subjects during HFO. In conclusion, HFO unmasks dissociation between insulin resistance and mitochondrial dysfunction in LBW subjects, suggesting that insulin resistance may be a cause, rather than an effect, of impaired muscle OXPHOS gene expression and mitochondrial dysfunction. Reduced increments in response to HFO of fasting plasma leptin, PP, and GIP levels may contribute to insulin resistance, lower satiety, and impaired insulin secretion in LBW subjects.     

Short-term, increasing dietary protein and fat moderately affect energy expenditure, substrate oxidation and uncoupling protein gene expression in rats

Macronutrient composition of diets can influence body-weight development and energy balance. We studied the short-term effects of high-protein (HP) and/or high-fat (HF) diets on energy expenditure (EE) and uncoupling protein (UCP1-3) gene expression. Adult male rats were fed ad libitum with diets containing different protein-fat ratios: adequate protein-normal fat (AP-NF): 20% casein, 5% fat; adequate protein-high fat (AP-HF): 20% casein, 17% fat; high protein-normal fat (HP-NF): 60% casein, 5% fat; high protein-high fat (HP-HF): 60% casein, 17% fat. Wheat starch was used for adjustment of energy content. After 4 days, overnight EE and oxygen consumption, as measured by indirect calorimetry, were higher and body-weight gain was lower in rats fed with HP diets as compared with rats fed diets with adequate protein content (P<.05). Exchanging carbohydrates by protein increased fat oxidation in HF diet fed groups. The UCP1 mRNA expression in brown adipose tissue was not significantly different in HP diet fed groups as compared with AP diet fed groups. Expression of different homologues of UCPs positively correlated with nighttime oxygen consumption and EE. Moreover, dietary protein and fat distinctly influenced liver UCP2 and skeletal muscle UCP3 mRNA expressions. These findings demonstrated that a 4-day ad libitum high dietary protein exposure influences energy balance in rats. A function of UCPs in energy balance and dissipating food energy was suggested. Future experiments are focused on the regulation of UCP gene expression by dietary protein, which could be important for body-weight management.