Rick H. Williams

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.

Influence of age and resistance exercise on human skeletal muscle proteolysis: a microdialysis approach

We combined the interstitial sampling method of microdialysis with the natural tracer qualities (i.e. non‐recyclability) of the amino acid 3‐methylhistidine (3MH) to uniquely study in vivo degradation of the two most abundant skeletal muscle proteins, myosin and actin. Interstitial 3MH concentration was measured before and for 24 h following a single bout of resistance exercise in eight young (27 ± 2 years) and eight old (75 ± 4 years) men. The exercise bout consisted of four exercises (3 sets of 8 repetitions at 80% one‐repetition maximum (1RM) per exercise) emphasizing the quadriceps. Interstitial 3MH concentration was calculated using the internal reference method from microdialysate samples that were obtained from two microdialysis probes placed in the vastus lateralis. Resting interstitial 3MH concentration was 44% higher (P < 0.05) in the old (6.16 ± 0.56 nmol ml−1) as compared with the young (4.28 ± 0.27 nmol ml−1). Interstitial 3MH was not different (P > 0.05) from preexercise at any time point within the 24 h following exercise in both the young and the old. Leg arteriovenous exchange measurements in a separate group of young subjects also showed no increase in 3MH release during the 4 h following a resistance exercise bout compared with a non‐exercised control leg (control leg: –28 ± 6, exercise leg: –28 ± 11 nmol min−1). These results suggest that myosin and actin proteolysis are not increased in the first 24 h following a standard bout of resistance exercise, and this response is not altered with ageing. The higher interstitial 3MH concentration in the old suggests an increased proteolysis of the two main contractile proteins in the rested and fasted state, which is consistent with a decrease in muscle mass with ageing. Microdialysis is an appropriate methodology for use in ageing individuals and is compatible with high‐intensity resistance exercise.

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.

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.

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.

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.

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.