Equivalent servings of free-range reindeer promote greater net protein balance compared to commercial beef.

Wild game consumption has been associated with health benefits but the acute influence on human protein metabolism remains unknown. We compared feeding-induced responses of equivalent amounts of free-range reindeer (FR) and commercial beef (CB) on protein kinetics using stable isotope methodology. Seven participants (age: 40 ± 14 years; body mass index: 24 ± 3 kg/m2) completed two randomised studies, ingesting 2 oz of FR or CB. L-[ring 2H5]phenylalanine & L-[ring 2H2]tyrosine were delivered via primed, continuous intravenous infusion. Blood samples were collected during the basal period and following consumption of FR or CB. Feeding-induced changes in whole-body protein synthesis (PS), protein breakdown (PB), and net protein balance (NB) were determined via plasma sample isotope enrichment analysis by gas chromatography-mass spectrometry; plasma essential amino acid (EAA) concentrations were determined by liquid chromatography-electrospray ionisation-mass spectrometry. Plasma post-prandial EAA concentrations were higher with FR compared to CB (P < 0.05). The acute feeding-induced PS response was not different, but PB was reduced and contributed to a superior level of NB (P < 0.00001) in FR compared to CB. Our results demonstrate that FR may influence more favourable protein metabolism than CB. These data support potential health benefits of wild game onf whole-body protein.Abbreviations: BMI: body mass index; DIAAS: digestible indispensable amino acid score; CB: commercial beef; EAA: essential amino acids; FR: free-range reindeer; Ra: rate of appearance; UAF: University of Alaska Fairbanks; USDA: USA Department of Agriculture.

Bed rest promotes reductions in walking speed, functional parameters, and aerobic fitness in older, healthy adults.

CONTEXT: The exact relationship between the bed rest-induced loss of skeletal muscle and reductions in muscle strength and physical performance in the older individuals is still unclear. OBJECTIVE: We examined the effect of 10 days of bed rest on changes in regional body composition, muscle strength, and functional status, and the relationship between these variables in older individuals. DESIGN, PARTICIPANTS, AND INTERVENTION: Regional body composition was measured using dual energy x-ray absorptiometry. We also determined changes in leg strength and several indices of functional status, including walking speed. RESULTS: Body weight, body mass index, and total and lower extremity lean mass decreased with bed rest. There were also significant reductions in knee extension one repetition maximum, isometric knee extension, knee extension 60° concentric, stair ascent time, stair ascent power, stair descent time, VO2 max, floor transfer test, 5-minute walk time, and chair stand. The overall change in total and lower extremity lean mass was also directly related to bed rest-induced reductions in one repetition maximum knee extension. CONCLUSIONS: Bed rest promoted overall declines in muscle mass, muscle strength, and physical function in older individuals. The changes in lean tissue were closely correlated with the bed rest-induced decline of muscle strength.

Acute lysine supplementation does not improve hepatic or peripheral insulin sensitivity in older, overweight individuals.

CONTEXT: Lysine supplementation may have a positive influence on the regulation of glucose metabolism but it has not been tested in the geriatric population. OBJECTIVE: We evaluated the impact of acute lysine supplementation using three randomized experimental scenarios: 1) oral glucose alone (control), 2) oral glucose and low-dose lysine (2 grams), and oral glucose and high dose lysine (5 grams) lysine in 7 older (66 ± 1 years/age), overweight/obese (BMI = 28 ± 2 kg/m(2)) individuals. METHODS: We utilized a dual tracer technique (i.e., [6,6-(2)H2] glucose primed constant infusion and 1-[(13)C] glucose oral ingestion) during an oral glucose tolerance test (OGTT) to examine differences in hepatic and peripheral insulin sensitivity under all three scenarios. RESULTS: Post-absorptive plasma glucose and insulin concentrations were not different between the three trials. Similarly, the response of glucose and insulin concentrations during the oral glucose tolerance tests (OGTT) was similar in the three trials. The results of the Matsuda index (ISI/M) were also not different between the three trials. As an index of hepatic insulin sensitivity, there were no significant differences in the endogenous glucose rate of appearance (glucose Ra) for control, 2 g lysine and 5 g lysine (1.2 ± 0.1, 1.1 ± 0.1, 1.3 ± 0.1 mg•kg(-1)•min(-1)), respectively. With respect to peripheral insulin sensitivity, there were no significant differences in the glucose rate of disappearance (glucose Rd) for control, 2 g lysine and 5 g lysine (4.2 ± 0.1, 4.3 ± 0.2, and 4.5 ± 0.4 mg•kg(-1)•min(-1)), respectively. CONCLUSIONS: Previous studies in younger participants have suggested that lysine may have a beneficial effect on glucose metabolism. However, acute lysine supplementation in the older population does not facilitate beneficial changes in glucose Ra or glucose Rd.

Bed rest worsens impairments in fat and glucose metabolism in older, overweight adults.

BACKGROUND: The effects of bed rest on the dysregulation of fatty acid and glucose metabolism have not been addressed in the older population. OBJECTIVE: We examined the effect of 10 days of bed rest on fatty acid kinetics and hepatic and peripheral insulin resistance in aging. METHODS: We utilized an octreotide, basal glucagon replacement, multistage insulin infusion, and the concomitant infusion of [6,6 (2)H2]glucose to derive insulin-mediated suppression of glucose production and insulin-stimulated glucose disposal in nine older, overweight individuals (body mass index 28.1 ± 1.7 kg m(-2); 39.9% ± 1.9% fat). During the multistage insulin infusion, we also infused [1-(13)C]palmitate to examine free fatty acid rate of appearance (R(a)). RESULTS: Body weight, % body fat, and energy metabolism did not change with bed rest. There was a significant decrease (-2291 ± 316 cm(3)) in visceral fat, and no change in abdominal subcutaneous fat with bed rest. Insulin-mediated suppression of glucose production was modest prior to bed rest and was further reduced (>15% ± 2%) by bed rest. There was also a minor decrease in the insulin-mediated suppression of free fatty acid R(a) after bed rest and, as a consequence, a small variation in plasma free fatty acid from pre- to post-bed rest in the first stage of the multistage insulin infusion. There was also a significant bed rest-induced decline (>2.0 ± 0.6 mg kg FFM(-1) min(-1)) in insulin-stimulated glucose disposal. CONCLUSIONS: Preexisting impairments in insulin sensitivity are worsened by bed rest and seem linked to alterations in the regulation of free fatty acid in older, overweight individuals.

EAA supplementation to increase nitrogen intake improves muscle function during bed rest in the elderly.

BACKGROUND & AIMS: Older individuals are more likely to experience extended hospitalization and become protein malnourished during hospitalization. The concomitant compulsory inactivity results in functional decline. Increasing protein intake in hospitalized patients improves nitrogen balance, but effects on function are unknown. In the present study, we examined the effects of increasing protein intake by essential amino acid (EAA) supplementation in older individuals subjected to 10 d bed rest on LBM and muscle function. METHODS: Subjects were given a placebo (n=12, 68+/-5 (SD) yrs, 83+/-19 kg) or 15 g of EAA (n=10, 71+/-6, 72+/-8 kg) 3 times per day throughout 10d of bed rest. LBM, muscle protein synthesis, and muscle function were determined before and after bed rest. Due to an imbalance in randomized gender distribution between groups, gender and beginning functional and LBM measures were utilized for analyses by repeated measures analysis of covariance (RMANCOVA). RESULTS: Analyses revealed the potential for the preservation of functional outcomes with EAA supplementation. CONCLUSIONS: Increasing protein intake above the RDA may preserve muscle function in the elderly during compulsory inactivity. EAA supplementation is potentially an efficient method of increasing protein intake without affecting satiety.

The impact of exercise training compared to caloric restriction on hepatic and peripheral insulin resistance in obesity.

CONTEXT: It has been difficult to distinguish the independent effects of caloric restriction versus exercise training on insulin resistance. OBJECTIVE: Utilizing metabolic feeding and supervised exercise training, we examined the influence of caloric restriction vs. exercise training with and without weight loss on hepatic and peripheral insulin resistance. DESIGN, PARTICIPANTS, AND INTERVENTION: Thirty-four obese, older subjects were randomized to: caloric restriction with weight loss (CR), exercise training with weight loss (EWL), exercise training without weight loss (EX), or controls. Based on an equivalent caloric deficit in EWL and CR, we induced matched weight loss. Subjects in the EX group received caloric compensation. Combined with [6,6(2)H(2)]glucose, an octreotide, glucagon, multistage insulin infusion was performed to determine suppression of glucose production (SGP) and insulin-stimulated glucose disposal (ISGD). Computed tomography scans were performed to assess changes in fat distribution. RESULTS: Body weight decreased similarly in EWL and CR, and did not change in EX and controls. The reduction in visceral fat was significantly greater in EWL (-71 +/- 15 cm(2)) compared to CR and EX. The increase in SGP was also almost 3-fold greater (27 +/- 2%) in EWL. EWL and CR promoted similar improvements in ISGD [+2.5 +/- 0.4 and 2.4 +/- 0.9 mg x kg fat-free mass (FFM)(-1) x min(-1)], respectively. CONCLUSIONS: EWL promoted the most significant reduction in visceral fat and the greatest improvement in SGP. Equivalent increases in ISGD were noted in EWL and CR, whereas EX provided a modest improvement. Based on our results, EWL promoted the optimal intervention-based changes in body fat distribution and systemic insulin resistance.

Influence of exercise intensity on abdominal fat and adiponectin in elderly adults.

To examine the influence of moderate-intensity (50% of VO(2peak)) exercise training (MI) versus high-intensity (75% of VO(2peak)) exercise training (HI) on regional fat distribution and plasma adiponectin, we randomized 18 overweight (body mass index [BMI] = 30 +/- 1 kg/m(2)) elderly (71 +/- 1 years) to HI, MI, or a control group (CON). Subjects enrolled in HI or MI completed a 12-week exercise training protocol designed to expend 1000 kcal/week. Body composition testing was completed prior to and following the exercise training using dual energy X-ray absorptiometry and a computed tomography scan. Plasma adiponectin was measured using enzymelinked immunoassay (ELISA). VO(2peak) improved in HI and MI, whereas there was no change in VO(2peak) in CON. No significant change in body weight, BMI, and % fat occurred in MI, HI, or CON. Although there was a significant reduction in visceral fat with HI (-39 cm(2)), there was no change in the MI or CON groups. In addition, there was a significant increase in thigh muscle attenuation in the HI group. There were no changes in thigh muscle attenuation in the MI and CON groups. Also, there was no change in plasma adiponectin in the MI, HI, or CON groups. In summary, our direct comparison of exercise intensity without weight loss promotes the efficacy of HI in the reduction in visceral fat, even without changes in adiponectin.

Visceral fat and adiponectin: associations with insulin resistance are tissue-specific in women.

Body fatness and its distribution are strongly and independently associated with peripheral insulin action. However, these associations are limited in their ability to predict the independent nature of hepatic and peripheral insulin resistance, especially in obese women. To define the relationships more precisely between regional fat distribution and adiponectin, and hepatic and peripheral insulin resistance, we studied 22 obese (43 +/- 0.1%) women who underwent a dual-energy X-ray absorptiometry scan and a computed tomography scan at the L4-L5 level. An octreotide (60 ng x kg(-1) x min(-1)), glucagon (0.65 ng x kg(-1) x min(-1)), and two-step insulin (0.25 mU x kg(-1) x min(-1) and 1.0 mU x kg(-1) x min(-1)) infusion was performed to quantify insulin-mediated suppression of hepatic glucose production (SGP) and insulin-stimulated glucose disposal (ISGD) in a simultaneous fashion. Hepatic glucose production (HGP) was measured using a primed, constant infusion of [6,6(2)H(2)] glucose. Mean plasma insulin increased from 5.6 +/- 0.1 microU/mL at baseline to 15.1 +/- 1.5 microU/mL in the first stage, and to 80.7 +/- 0.5 microU/mL in the second stage. Although there was no significant relationship between visceral adipose tissue (VAT) and basal HGP (r = 0.34, p = 0.117), there was a significant inverse correlation (r = -0.67, p = 0.003) between VAT and SGP. There was a significant correlation (r = 0.55, p = 0.008) between adiponectin and ISGD. In conclusion, these data support: (1) the inability of basal glucose metabolism to accurately reflect hepatic insulin resistance, (2) the deleterious role of VAT in the development of insulin resistance in the liver, and (3) provide additional support for the positive influence of adiponectin against peripheral insulin resistance in obese, postmenopausal women.

Exercise-induced changes in insulin action and glycogen metabolism in elderly adults.

PURPOSE: Although data suggest that physical activity is associated with decreased insulin resistance, recommendations for exercise training are not specific for age or level of obesity. Therefore, we examined the influence of moderate-intensity (50% of VO2max) exercise training (MI) versus high-intensity (75% of VO2max) exercise training (HI) on insulin-stimulated glucose disposal (ISGD) in elderly individuals. METHODS: Following medical examinations, 21 overweight (body mass index = 29 +/- 1 kg x m(-2)) elderly (74 +/- 1 yr) subjects were randomized to 1) HI, 2) MI, or a 3) nonexercising control group. Subjects enrolled in HI or MI completed a 12-wk exercise training regimen designed to expend 1000 kcal x wk. ISGD was assessed using a hyperinsulinemic, euglycemic clamp pre- and postintervention. ISGD was corrected for hepatic glucose production (glucose Ra) using a constant rate infusion of [6,6-H2]glucose and determined during the last 30 min of the clamp by subtracting glucose Ra from the exogenous glucose infusion rate. Nonoxidative glucose disposal was calculated using indirect calorimetry. Body composition testing was completed using dual energy x-ray absorptiometry. RESULTS: ISGD increased by approximately 20% with HI (Delta of 1.4 +/- 0.5 mg x kg(-1) FFM.min(-1)). However, ISGD did not change (Delta of -0.4 +/- 0.1 mg x kg(-1) FFM.min(-1)) with MI and was not different (Delta of -0.2 +/- 0.1 mg x kg(-1) FFM.min(-1)) in the control group. Nonoxidative glucose disposal increased with HI (Delta of 1.4 +/- 0.5 mg x kg(-1) FFM.min(-1)), but there was no change in nonoxidative glucose disposal with MI or in the control group. No change in body weight or percentage of body fat was observed in any group. CONCLUSION: In weight-stable subjects, MI resulted in no change in ISGD, and the improvement in ISGD with HI was completely reliant on improvements in nonoxidative glucose disposal.

Effects of an ad libitum, high carbohydrate diet and aerobic exercise training on insulin action and muscle metabolism in older men and women.

BACKGROUND: Previous studies have demonstrated that aerobic exercise training and weight loss have independent effects on insulin-stimulated glucose disposal (ISGD). We hypothesized that ad libitum consumption of a high-carbohydrate diet would result in weight loss and improved ISGD, and that aerobic exercise training would facilitate greater improvements in ISGD compared with diet alone. METHODS: Older participants (13 women, 9 men; age = 66 +/- 1 year) with impaired glucose tolerance were randomly assigned to an ad libitum diet alone (18% fat, 19% protein, 63% carbohydrate) or this diet plus aerobic exercise training (4 d/wk, 45 min/d, 80% VO(2peak)) for 12 weeks. ISGD, abdominal fat distribution, muscle glycogen, and glycogen synthase activity were assessed pre- and postintervention. RESULTS: Consumption of the diet resulted in significant weight loss and an improvement in ISGD. Consumption of the diet plus exercise training also resulted in weight loss and increased ISGD, but results were not significantly different from those in the diet-alone group. Mean abdominal visceral and subcutaneous adipose tissue cross-sectional areas were smaller postintervention compared to baseline with no difference between groups. Exercise training and consumption of the diet increased muscle glycogen content (344.7 +/- 21.3 to 616.7 +/- 34.4 micromol.g(-1)) and decreased glycogen synthase activity (0.21 +/- 0.02 to 0.13 +/- 0.01) compared to the diet alone. CONCLUSIONS: These results demonstrate that consumption of an ad libitum, high-carbohydrate diet alone or in combination with aerobic exercise training results in weight loss and improved insulin sensitivity. Furthermore, exercise combined with this diet appears to limit additional increases in insulin sensitivity due to muscle glycogen supercompensation with a concomitant adaptive response of glycogen synthase.

Human soleus and vastus lateralis muscle protein metabolism with an amino acid infusion.

The calf muscles, compared with the thigh, are less responsive to resistance exercise in ambulatory and bed-rested individuals, apparently due to muscle-specific differences in protein metabolism. We chose to evaluate the efficacy of using amino acids to elevate protein synthesis in the soleus, because amino acids have been shown to have a potent anabolic effect in the vastus lateralis. Mixed muscle protein synthesis in the soleus and vastus lateralis was measured before and after infusion of mixed amino acids in 10 individuals (28 +/- 1 yr). Phosphorylation of ribosomal protein p70 S6 kinase (p70S6K; Thr389) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1; Thr37/46) was also evaluated at rest and after 3 h of amino acid infusion. Basal protein synthesis was similar (P = 0.126), and amino acids stimulated protein synthesis to a similar extent (P = 0.004) in the vastus lateralis (0.043 +/- 0.011%/h) and soleus (0.032 +/- 0.017%/h). Phosphorylation of p70S6K (P = 0.443) and 4E-BP1 (P = 0.192) was not increased in either muscle; however, the soleus contained more total (P = 0.002) and phosphorylated (P = 0.013) 4E-BP1 than the vastus lateralis. These data support the need for further study of amino acid supplementation as a means to compensate for the reduced effectiveness of calf resistance exercise in ambulatory individuals and those exposed to extended periods of unloading. The greater 4E-BP1 in the soleus suggests that there is a muscle-specific distribution of general translational initiation machinery in human skeletal muscle.