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Whereas diet-induced obese rabbits have been used to study various aspects of obesity, alterations of lipid metabolism in this model have not been clarified. This study aimed to compare plasma nonesterified fatty acid (NEFA) and triglyceride (TG) kinetics in obese and lean rabbits by means of [U.sup.-13][C.sub.16]-palmitate infusion. Young female rabbits consumed either a high-fat diet (49% energy from fat) ad libitum to develop obesity (n = 6) or a normal diet (7.9% energy from fat) as lean control (n = 5). After 10 wk of feeding, the body weight of obese rabbits (5.33 [+ or -] 0.05 kg) was greater (P< 0.001 ) than that of lean rabbits (3.89 [+ or -] 0.07 kg). The obese rabbits had higher concentrations of plasma NEFA and TG and a greater rate of fatty acid (FA) turnover. Whereas the fractional secretion rates of hepatic TG did not differ, 100% of hepatic secretory TG was synthesized from plasma NEFA in the lean rabbits compared to 59% in the obese rabbits (P < 0.001). In the lean rabbits, hepatic lipase-mediated hydrolysis of lipoprotein TG did not contribute to the FA pool for synthesis of secretory TG, consistent with the naturally occurring deficit in hepatic lipase in this species. We conclude that lipid metabolism in dietinduced obese rabbits is similar to that in obese humans. The deficiency in hepatic lipase in rabbits simplifies the quantitation of hepatic lipid kinetics.

Timing of nutrient ingestion has been demonstrated to influence the anabolic response of muscle following exercise. Previously, we demonstrated that net amino acid uptake was greater when free essential amino acids plus carbohydrates were ingested before resistance exercise rather than following exercise. However, it is unclear if ingestion of whole proteins before exercise would stimulate a superior response compared with following exercise. This study was designed to examine the response of muscle protein balance to ingestion of whey proteins both before and following resistance exercise. Healthy volunteers were randomly assigned to one of two groups. A solution of whey proteins was consumed either immediately before exercise (PRE; n = 8) or immediately following exercise (POST; n = 9). Each subject performed 10 sets of 8 repetitions of leg extension exercise. Phenylalanine concentrations were measured in femoral arteriovenous samples to determine balance across the leg. Arterial amino acid concentrations were elevated by ~50%, and net amino acid balance switched from negative to positive following ingestion of proteins at either time. Amino acid uptake was not significantly different between PRE and POST when calculated from the beginning of exercise (67 [+ or -] 22 and 27 [+ or -] 10 for PRE and POST, respectively) or from the ingestion of each drink (60 [+ or -] 17 and 63 [+ or -] 15 for PRE and POST, respectively). Thus the response of net muscle protein balance to tinting of intact protein ingestion does not respond as does that of the combination of free amino acids and carbohydrate. muscle protein synthesis; arteriovenous balance; net muscle protein balance; muscle biopsies

This study was designed to evaluate the effects of enriching an essential amino acid (EAA) mixture with leucine on muscle protein metabolism in elderly and young individuals. Four (2 elderly and 2 young) groups were studied before and after ingestion of 6.7 g of EAAs. EAAs were based on the composition of whey protein [26% leucine (26% Leu)] or were enriched in leucine [41% leucine (41% Leu)]. A primed, continuous infusion of L-[[ring-.sup.2][H.sub.5]]phenylalanine was used together with vastus lateralis muscle biopsies and leg arteriovenous blood samples for the determinations of fractional synthetic rate (FSR) and balance of muscle protein. FSR increased following amino acid ingestion in both the 26% (basal: 0.048 [+ or -] 0.005%/h; post-EAA: 0.063 [+ or -] 0.007%/h) and the 41% (basal: 0.036 [+ or -] 0.004%/h; post-EAA: 0.051 [+ or -] 0.007%/h) Leu young groups (P < 0.05). In contrast, in the elderly, FSR did not increase following ingestion of 26% Leu EAA (basal: 0.044 + 0.003%/13; post-EAA: 0.049 [+ or -] 0.006%/h; P > 0.05) but did increase following ingestion of 41% Leu EAA (basal: 0.038 +0.007%/h; post-EAA: 0.056 [+ or -] 0.008%/h; P < 0.05). Similar to the FSR responses, the mean response of muscle phenylalanine net balance, a reflection of muscle protein balance, was improved (P < 0.05) in all groups, with the exception of the 26% Leu elderly group. We conclude that increasing the proportion of leucine in a mixture of EAA can reverse an attenuated response of muscle protein synthesis in elderly but does not result in further stimulation of muscle protein synthesis in young subjects. nutrition; sarcopenia; stable isotopes doi:10.1152/ajpendo.00488.2005

We describe a method based on the traditional arteriovenous balance technique in conjunction with muscle biopsies for the determination of leg muscle protein balance during the nonsteady state in blood amino acid concentrations. Six young, healthy individuals were studied in the postabsorptive state (pre-Phe) and after a bolus ingestion of ~0.5 g phenylalanine (post-Phe). Post-Phe free phenylalanine concentrations in blood and muscle increased (P < 0.05), but the respective concentrations of the amino acid threonine did not change. The average post-Phe leg net balance (NB) for threonine decreased from basal (P < 0.05), but that for phenylalanine did not change. A volume of distribution for free phenylalanine in the leg was calculated based on the leg lean mass and the relative muscle water content and used to estimate the rate of accumulation of free phenylalanine in the leg. When the post-Phe NB for phenylalanine was corrected for the rate of accumulation of free phenylalanine in the leg, the post-Phe NB for phenylalanine decreased from basal (P < 0.05). This corrected value was not different (P > 0.05) from the value predicted for the phenylalanine NB based on the pre- and post-Phe NB responses for threonine. We conclude that the protein NB in non-steady-state blood phenylalanine concentrations can be determined from the arteriovenous phenylalanine NB by accounting for changes in free phenylalanine within its volume of distribution. methodology; phenylalanine net balance; intracellular phenylalanine; volume of distribution

We sought to determine whether ingestion of a between-meal supplement containing 30 g of carbohydrate and 15 g of essential amino acids (CAA) altered the metabolic response to a nutritionally mixed meal in healthy, recreationally active male volunteers. A control group (CON; n = 6, 38 [+ or -] 8 yr, 86 [+ or -] 10 kg, 179 [+ or -] 3 cm) received a liquid mixed meal [protein, 23.4 [+ or -] 1.0 g (essential amino acids, 14.7 [+ or -] 0.7 g); carbohydrate, 126.6 [+ or -] 4.0 g; fat, 30.3 [+ or -] 2.8 g] every 5 h (0830, 1330, 1830). The experimental group (SUP; n = 7, 36 [+ or -] 10 yr, 87 [+ or -] 12 kg, 180 [+ or -] 3 cm) consumed the same meals but, in addition, were given CAA supplements (1100, 1600, 2100). Net phenylalanine balance (NB) and fractional synthetic rate (FSR) were calculated during a 16-h primed constant infusion of L-[ring-[sup.2]Hs]phenylalanine. Ingestion of a combination of CAA supplements and meals resulted in a greater mixed muscle FSR than ingestion of the meals alone (SUP, 0.099 [+ or -] 0.008; CON, 0.076 [+ or -] 0.005%/h; P < 0.05). Both groups experienced an improvement in NB after the morning (SUP, -2.2 [+ or -] 3.3; CON, -1.5 [+ or -] 3.5 nmol x [min.sup.-1] x 100 ml leg [volume.sup.-1]) and evening meals (SUP, -9.7 [+ or -] 4.3; CON, -6.7 [+ or -] 4.1 nmol x [min.sup.-1] x 100 ml leg [volume.sup.-1]). NB after CAA ingestion was significantly greater than after the meals, with values of 40.2 [+ or -] 8.5 nmol x [min.sup.-1] 100 ml leg [volume.sup.-1]. These data indicate that CAA supplementation produces a greater anabolic effect than ingestion of intact protein but does not interfere with the normal metabolic response to a meal. protein metabolism; diet; supplement; skeletal muscle

We recently demonstrated that muscle protein synthesis was stimulated to a similar extent in young and elderly subjects during a 3-h amino acid infusion. We sought to determine if a more practical bolus oral ingestion would also produce a similar response in young (34 [+ or -] 4 yr) and elderly (67 [+ or -] 2 yr) individuals. Arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 [micro]mol/kg) constant infusion (0.05 [micro]mol x [kg.sup.-1] x [min.sup.-1]) of L-[ring-[sup.2][H.sub.5]]phenylalanine. Muscle protein kinetics and mixed muscle fractional synthetic rate (FSR) were calculated before and after the bolus ingestion of 15 g of essential amino acids (EAA) in young (n = 6) and elderly (n = 7) subjects. After EAA ingestion, the rate of increase in femoral artery phenylalanine concentration was slower in elderly subjects but remained elevated for a longer period. EAA ingestion increased FSR in both age groups by ~0.04%/h (P < 0.05), However, muscle intracellular (IC) phenylalannie concentration remained significantly higher in elderly subjects at the completion of the study (young: 115.6 [+ or -] 5.4 nmol/ml; elderly: 150.2 [+ or -] 19.4 nmol/ml). Correction for the free phenylalanine retained in the muscle IC pool resulted in similar net phenylalanine uptake values in the young and elderly. EAA ingestion increased plasma insulin levels in young (6.1 [+ or -] 1.2 to 21.3 [+ or -] 3.1 [micro]IU/ml) but not in elderly subjects (3.0 [+ or -] 0.6 to 4.3 [+ or -] 0.4 [micro]IU/ml). Despite differences in the time course of plasma phenylalanine kinetics and a greater residual IC phenylalanine concentration, amino acid supplementation acutely stimulated muscle protein synthesis in both young and elderly individuals. aging; supplementation; nutrition; sarcopenia

Research shows that more human muscle protein synthesis occurs after a period of resistance exercise. Fractional synthesis and fractional breakdown rates were measured in male and female subjects for two days after concentric or eccentric activity. The net protein balance increased steadily during this time. Some protein degradative activity also occurred after the exercise causing a reduction in cytoskeletal proteins.

Different mass isotopomer dilution tracer methods give the same precursor enrichment and fractional synthesis rate of plasma very low density lipoprotein-palmitate from acetyl-CoA in postabsorptive humans. The precursor enrichments are deduced indirectly from the product pool enrichments. Improving the accuracy of the isotopic ratio measurements and infusing (1,2-13C)acetate instead of (1-13C)acetate reduces the systematic biases involved in the singly and doubly labeled enrichments.

Abstract Background Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma. Methods A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-α agonist treatment. Results Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively) after PPAR-α agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-α treatment (P = 0.002). However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-θ activation during hyper-insulinemia decreased significantly following PPAR-α treatment. Conclusion PPAR-α agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.

This study tests the hypotheses that (a) a mixture of whey protein, amino acids (AA), and carbohydrates (CHO) stimulates net muscle protein synthesis to a greater extent than isoenergetic CHO alone after resistance exercise; and (b) that the stimulatory effect of a protein, AA, and CHO mixture will last beyond the 1st hour after intake. Eight subjects participated in 2 trials. In one (PAAC), they ingested 77.4 g CHO, 17.5 g whey protein, and 4.9 g AA 1 hr after resistance exercise. In the other (CON), 100 g CHO was ingested instead. They received a primed constant infusion of L-[²H[sub5]]-phenylalanine, and samples from femoral artery and vein, and biopsies from vastus lateralis were obtained. The area under the curve for net uptake of phenylalanine into muscle above predrink value was 128 ± 42 mg ⋅ leg[sup-1] (PAAC) versus 32 ± 10 mg ⋅ leg[sup-1]) (CON) for the 3 hr after the drink (p = .04). The net protein balance response to the mixture consisted of two components, one rapid immediate response, and a smaller delayed response about 90 min after drink, whereas in CON only a small delayed response was seen. We conclude that after resistance exercise, a mixture of whey protein, AA, and CHO stimulated muscle protein synthesis to a greater extent than isoenergetic CHO alone. Further, compared to previously reported findings, the addition of protein to an AA + CHO mixture seems to extend the anabolic effect. [ABSTRACT FROM AUTHOR]