Reduction In Lean Body Mass Research Articles

A gripping reality: oxidative stress, inflammation, and the pathway to frailty

clinical investigators within the field of geriatric medicine aim to get a handle on “frailty.” That aging is an inevitable consequence of staying alive is irrefutable, but why some people manage to do so and maintain stature and function, while others do not, remains an unresolved question.

Interleukin-6 inhibits growth hormone-mediated gene expression in hepatocytes

During systemic inflammation, the liver becomes unresponsive to growth hormone (GH), resulting in decreased plasma insulin-like growth factor-I (IGF-I) with concomitant reductions in lean body mass. Transgenic mice that overexpress IL-6 also demonstrate impaired growth and decreased IGF-I. To determine whether IL-6 directly inhibits GH-inducible gene expression, CWSV-1 hepatocytes were incubated with IL-6 (10 ng/ml), then stimulated with recombinant human GH (500 ng/ml, 18 h). The increase in IGF-I and serine protease inhibitor 2.1 (Spi 2.1) mRNA in GH-treated cells was inhibited by treatment with IL-6 for 24 h. To investigate potential mechanisms, we examined the effects of IL-6 on GH receptor (GHR) expression and GH signaling via the JAK/signal transducer and activator of transcription (STAT) and MAP kinase pathways. Incubation of cells with IL-6 (10 ng/ml, 24 h) had no effect on GHR abundance or signaling proteins JAK2, STAT5b, and ERK1/2. Although GH transiently increased (2- to 5-fold) the tyrosine phosphorylation of GHR, JAK2, STAT5b, and ERK1/2, IL-6 did not alter these phosphorylation events. However, nuclear protein from IL-6-treated cells demonstrated reduced STAT5 DNA binding (by EMSA) at 15 min (-20%) and 60 min (-43%) after GH stimulation. To determine whether IL-6 inhibits GH-inducible promoter activity, CWSV-1 cells were transfected with Spi 2.1 or prolactin receptor promoter luciferase vectors, incubated with or without IL-6, then stimulated with GH. The induction of both Spi 2.1 (7.5-fold) and prolactin receptor (4-fold) promoter activity by GH was inhibited by IL-6. In summary, IL-6 mediates hepatic GH resistance by a time-dependent inhibition of GH-inducible promoter activity that is associated with reductions in STAT5 DNA binding.

Central CART gene delivery by recombinant AAV vector attenuates body weight gain in diet-induced-obese rats

Cocaine- and amphetamine-regulated transcript (CART) peptide is a neuro-peptide implicated in the regulation of energy homeostasis. CART mRNA and its encoded peptide have been found in many brain regions that regulate energy balance. To investigate the effects of chronic central expression of CART in the diet-induced-obese (DIO) rats, we constructed and packaged recombinant adeno-associated virus (AAV) 2 vector containing rat CART cDNA and a reporter gene encoding green fluorescence protein (AAV-rCART-hrGFP) driven by the CMV promoter. Approximately 1 × 10 11 particles of AAV-rCART-hrGFP or control vector AAV-IRES-hrGFP (AAV-hrGFP in short) were injected through intracerebroventricular (ICV) cannulas into adult male DIO Long–Evans rats. Throughout the 7-month study period, AAV-rCART-hrGFP-injected rats had a significantly decreased food intake and body weight gain when compared with those of AAV-hrGFP-injected rats. AAV-rCART-hrGFP injection also modulated hyperphagia following a 24-hour fasting in these rats. Body composition analysis indicated that decreased body weight gain was due to reduction in lean body mass while fat mass was not affected. Expression of green fluorescence protein (GFP) suggested that recombinant AAV virions are located at cells surrounding the third ventricle and medial eminence. Our results demonstrate that chronic expression of CART in brain can modulate energy intake in diet-induced-obese rats. The CART pathway plays an important role in body mass regulation in DIO rats.

Maintaining Endurance Performance At High Altitude (4300 M) Despite Severe Energy Intake Deficit

Body weight (BW) and lean body mass (LBM) of sea-level (SL) residents are typically reduced by <4% and <2%, respectively, while endurance performance is greatly impaired initially but then improves during the first three weeks of altitude exposure. PURPOSE: To determine if a greater reduction in LBM due to severe energy intake deficit will eliminate the performance improvement despite maintenance of a high carbohydrate (CHO) diet METHODS: Two groups of men (mean ± SE: 22 ± 1 yrs) were matched at SL on cycle peak oxygen uptake (VO2peak), cycle endurance performance (50% of VO2 for 50 min followed by 70% of VO2peak to exhaustion), total energy intake, and percent of energy from CHO (%CHO). At ALT, the deficit group (DEF, n = 10) consumed 1340 kcal/day (−40%) below BW maintenance requirements and the adequately fed group (ADQ, n = 7) ingested enough energy to maintain BW. Both groups ingested similar %CHO (∼64 to 71%) and >347 g of CHO/day at SL and ALT. Endurance performance was again assessed at ALT on days 1 and 18 using the identical absolute power outputs that were used at SL for 50% (149 ± 4 watts) and 70% (218 ±6 watts) VO2peak. RESULTS: From SL to day 18 at ALT, BW was reduced for DEF (80.4 ± 12 to 74.3 ± 3 kg;-8 ± 2%; P < 0.01) but not ADQ (74.4 ±3 to 73.3 ±3 kg; −1 ± 1%). Similarly, LBM (estimated from circumference measures) was reduced for DEF (71.0 ± 10 to 66.4 ± 7 kg, −6 ± 1%; P < 0.01) but not ADQ (66.3 ± 5 to 64.9 ± 5 kg; −2 ± 1%). On either day at ALT, there was no difference between groups in endurance time. For both groups, endurance performance at ALT was 6 ± 2% greater on day 18 (57 ± 2 min) than on day 1 (54 ± 1 min; P < 0.012). CONCLUSION: During the first three weeks of ALT acclimatization, a 6% loss in LBM due to underfeeding did not adversely affect the improvement in endurance performance. The lack of effect on performance during severe energy deficit may have been due to the maintenance of muscle glycogen stores or a lower rate of muscle glycogen utilization for the same amount of work.

Inhibition of 11β-hydroxysteroid dehydrogenase type 1 reduces food intake and weight gain but maintains energy expenditure in diet-induced obese mice

The 11beta-hydroxysteroid dehydrogenase type-1 inhibitor BVT.2733 lowers blood glucose and insulin in mutant mouse models of obesity and diabetes. Its effects on energy balance and body composition, and their contribution to improved glucose homeostasis have received little attention. BVT.2733 (100 mg/kg, orally) was given twice daily to lean and diet-induced obese mice for 16 or 17 days. A group of obese mice was pair-fed to the amounts consumed by BVT.2733-treated mice. In both obese and lean mice, BVT.2733 reduced food intake and weight gain, but increased water intake. Pair-feeding caused almost as great a decrease in body weight as BVT.2733. Energy expenditure was 38+/-8% higher in the BVT.2733-treated obese mice than in the pair-fed mice. Terminal plasma corticosterone was raised, lean body weight reduced and percentage fat unchanged in the pair-fed mice (control, 47.8+/-2.6%; pair-fed, 47.1+/-1.9%), whereas BVT.2733 did not reduce lean mass, but did reduce percentage fat (40.9+/-2.0%). BVT.2733 but not pair-feeding reduced both the glucose tolerance AUC and the plasma insulin concentration 30 min after giving glucose. BVT.2733 reduced food intake but prevented a concomitant reduction in lean body mass and energy expenditure. The latter effects may have contributed to improved glucose tolerance.

497. Central CART Gene Delivery by Recombinant AAV Vector Decreases Lean Body Mass in Diet-Induced Obese Male Rats

Cocaine- and amphetamine-regulated transcript (CART) peptide is a neuro-peptide implied in the regulation of energy homeostasis. CART mRNA and its encoded peptide have been localized in many brain regions that regulate energy balance. To study the physiological function of CART in the diet-induced obese (DIO) rats, we constructed and packaged recombinant adeno-associated virus 2 (AAV) vector containing CMV promoter driven rat CART cDNA and a reporter gene hrGFP (AAV-rCART-hrGFP). Approximately 1x1011 particles of AAV-rCART-hrGFP or control vector AAV-IRES- hrGFP were injected through intra-cerebro-ventricular (ICV) into 100 days old male DIO Long-Evans rats (n=9). Starting on three days post-injection, AAV-rCART-hrGFP-injected rats significantly decreased food intake and body weight gain when compared with that of AAV-IRES-hrGFP-injected rats. AAV-rCART-hrGFP injection modulated hyperphagia following overnight fasting in these rats. Body composition analysis indicated that decreased body weight was due to reduction in lean body mass while fat mass was not different from the control animals. Expression of green fluorescence protein (GFP) suggested that recombinant AAV virions are located at cells around the 3rd ventricle, paraventricle nuclei and medial eminence, external. Our results demonstrate that chronic over- expression of CART in brain can decrease body lean mass by inducing negative energy balance in rats. Cocaine- and amphetamine-regulated transcript (CART) peptide is a neuro-peptide implied in the regulation of energy homeostasis. CART mRNA and its encoded peptide have been localized in many brain regions that regulate energy balance. To study the physiological function of CART in the diet-induced obese (DIO) rats, we constructed and packaged recombinant adeno-associated virus 2 (AAV) vector containing CMV promoter driven rat CART cDNA and a reporter gene hrGFP (AAV-rCART-hrGFP). Approximately 1x1011 particles of AAV-rCART-hrGFP or control vector AAV-IRES- hrGFP were injected through intra-cerebro-ventricular (ICV) into 100 days old male DIO Long-Evans rats (n=9). Starting on three days post-injection, AAV-rCART-hrGFP-injected rats significantly decreased food intake and body weight gain when compared with that of AAV-IRES-hrGFP-injected rats. AAV-rCART-hrGFP injection modulated hyperphagia following overnight fasting in these rats. Body composition analysis indicated that decreased body weight was due to reduction in lean body mass while fat mass was not different from the control animals. Expression of green fluorescence protein (GFP) suggested that recombinant AAV virions are located at cells around the 3rd ventricle, paraventricle nuclei and medial eminence, external. Our results demonstrate that chronic over- expression of CART in brain can decrease body lean mass by inducing negative energy balance in rats.

P0624 LIVER GROWTH HORMONE RESISTANCE PRECEDES GROWTH FAILURE IN EXPERIMENTAL COLITIS

Introduction: The combined effects of circulating cytokines and reduced caloric intake may cause growth hormone (GH) resistance in children with Crohn’s disease. Anabolic effects of GH are mediated via phosphorylation of the STAT5b transcription factor and subsequent up regulation of IGF-1 gene expression. The molecular basis for GH resistance in colitis was not known. We hypothesized that liver GH dependent phosphorylation of STAT5b would be impaired in colitis, and that this would precede growth failure. Methods: Interleukin 10 (IL-10) null mice on the C3H/HejBir background develop chronic colitis beginning at 4–6 weeks of age. Growth, body composition, and GH signaling in liver and skeletal muscle were characterized in IL-10 null mice and wild type (WT) littermates at 8 and 20 weeks of age. Results: Colitis was present in both sexes by 8 weeks of age. Maximal reductions in growth and body composition were observed in both sexes by 20 weeks of age; these were first apparent in male mice at 8 weeks. As expected, liver IGF-1 expression was reduced in colitic mice. This was associated with a significant reduction in nuclear phospho-STAT5 abundance at both 8 and 20 weeks, and down regulation of GH receptor (GHR) abundance. Down regulation of liver GHR expression was associated with reduced nuclear abundance and DNA binding of the GHR gene promoter transactivator, Sp3. By comparison, skeletal muscle STAT5 phosphorylation was relatively preserved in colitic mice, despite reductions in lean body mass in males. Tumor Necrosis Factor (TNF) pre-treatment of rat H4IIE hepatoma cells and C2C12 mouse myoblast cells reduced GHR abundance and impaired GH dependent STAT5 activation in the liver, but not muscle, cell line. Conclusion: Growth failure and reduced IGF-1 expression in experimental colitis were associated with down regulation of liver GHR abundance and impaired STAT5 phosphorylation. The defect in liver STAT5 phosphorylation occurred early in the course of colitis, coincident with the onset of reduced weight gain, and was reproduced by TNF treatment in a liver cell line. Therapies which block TNF may improve growth in children with Crohn’s disease in part by restoring hepatic GH signaling and IGF-1 expression.

Adults with partial growth hormone deficiency have an adverse body composition.

The current biochemical definition of severe GH deficiency (stimulated peak GH < 3 micro g/liter) provides good separation of GH-deficient (GHD) adults from normal subjects, although it may not account for all patients with impaired GH secretion. The vast majority of normal subjects display a peak GH level in excess of 7 micro g/liter in response to the insulin tolerance test. Using a peak GH response of 7 micro g/liter as an arbitrary upper limit, we investigated the effects of partial GH deficiency (GH insufficiency, GHI; peak GH response of 3-7 micro g/liter) on the body composition of hypopituitary adults. GHD adults (n = 30, peak GH < 3 micro g/liter) were of shorter stature than the controls. Body mass index was not significantly increased, but waist/hip ratio (0.885 vs. 0.818, P = 0.001) and skinfold thickness (78.2 vs. 59.6 mm, P = 0.003) were greater than control subjects. Bioimpedance analysis revealed these patients to have reduced lean body mass (LBM) (44.4 vs. 51.2 kg, P = 0.023) and increased fat mass (FM) (25.7 vs. 18.4 kg, P = 0.039). Dual-energy x-ray absorptiometry (DXA) analysis of body composition confirmed reduced LBM (43.6 vs. 50.6 kg, P = 0.010) and increased FM (26.0 vs. 19.2 kg, P = 0.015). The excess FM was observed to be primarily truncal in distribution. Similarly, GHI adults were of shorter stature but with increased waist/hip ratio (0.871 vs. 0.818, P = 0.006) and skinfold thickness (80.8 vs. 59.6 mm, P = 0.003), compared with controls. Bioimpedance analysis revealed a reduction in LBM (44.9 vs. 51.2 kg, P = 0.020). DXA studies confirmed the reduced LBM (45.0 vs. 50.6 kg, P = 0.041) and additionally noted an increase in percent FM (32.9 vs. 27.4%, P = 0.019). All measures of body composition in the GHI patients were intermediate between those of the controls and GHD patients. Serum leptin levels were significantly elevated in both the GHD (41.5 vs. 20.7 ng/ml, P = 0.009) and GHI (36.7 vs. 20.7 ng/ml, P = 0.022) adults, compared with healthy controls. The excess FM observed using DXA in the GHD and GHI adults equated to 6.5 kg (8%) and 3.5 kg (5.5%), respectively, relative to healthy controls. In summary, we have shown that adults with GHI have abnormalities of body composition characteristic of GHD. The degree of abnormality of body composition lies between that of healthy subjects and GHD adults and correlates with the IGF-I level. Any future trials of GH replacement in patients with GHI must await further studies to establish the exact impact of this relative deficiency on the broad spectrum of biological end points influenced by GH status.

Altered Body Composition Affects Resting Energy Expenditure and Interpretation Of Body Mass Index In Chiloren With Spinal Cord Injury

Background: lndividuals with spinal cord injury (SCI) typically undergo changes in their body composition (reduction in lean body mass and an increase in fat mass) that can Iead to secondary complications associated with diminished physical activity and obesity.Methods: This study used dual energy X-ray absorptiometry (DXA) to estimate the totallean tissue mass (L TM), total body fat, and total bone mineral content (BMC) to assess the relationship between body mass index (BMI), body composition, and resting metabolic rate (RMR) in a group of children with SCI who were matched with able-bodied controls for age and sex. Body composition and RMR were measured in 18 boys and 9 girls (1 0-21 years of age) who had a SCI in the previous 1 to 3 years andin 27 age-and sex-matched controls.Results: Children with SCI had significantly lower mean LTM than control subjects (3 7.6 ± 9.6 kg and 46.7 ± 9.2 kg, respectively; P < 0.001) and higher percent body fat (26.4 ± 7.9% and 20.2 ± 8.5%, respectively; P < 0.02) as measured by DXA, despite their reduced BMI (1 8.9 ± 3.8 kg/m2 and 21.2 ± 2.9 kg/m2 , respectively; P < 0.01 ). Children with SCI had lower RMR than the controls subjects (1213 ± 334 kj/d and 1511 ± 257 kj/d, respectively), but there was no difference in RMR when adjusted for LTM.Conclusion: Children with SCI have lower RMRs that are associated with their reduced LTM. The reduction in LTM and RMR may predispose children with SCI to relative gains in body fat. BMI significantly underestimates body fat in children with SCI.

EXERCISE-INDUCED HYPOHYDRATION AND ISOKINETIC MUSCULAR STRENGTH AND ENDURANCE

There has long been an interest in the deleterious effects of hypohydration on exercise. The majority of the research pertaining to hypohydration and muscular performance has focused on isometric and isotonic strength and endurance and the results are inconclusive. Furthermore, little has been done using isokinetic measures. PURPOSE: This investigation was done in an attempt to examine the extent to which exercise-induced hypohydration affects isokinetic muscular strength and endurance. METHODS: Nine moderately fit males performed a Thorstensson Fatigue Test using the quadriceps muscle group of the dominant leg 3-h after completing an exercise-induced dehydration (DT) and rehydration (RT) protocol. DT consisted of 100 min of low intensity exercise in a vinyl sweatsuit combined with fluid restriction during exercise and recovery. RT was identical to DT except participants were encouraged to rehydrate using water during both exercise and recovery. Peak torque values were used as the measure of muscular strength (MS), while muscular endurance was quantified using a fatigue index (FI). Hydration status was assessed using practical measures that included body weight change and urine specific gravity. RESULTS: Mean weight loss during DT and RT, was 3.46% and 1.29% lean body mass (LBM), respectively. MS, FI, and blood lactate concentration were not different (P > .05) between trials. Mean (± SE) MS for DT and RT was, 125.2 ± 6.9 and 127.9 ± 7.0ft-lbs, respectively. Mean (± SE) FI for DT and RT was, 66 ± 6.6 and 65.5 ± 7.7%, respectively. CONCLUSIONS: A 3.46% reduction in LBM following DT did not significantly affect MS or FI when compared to RT. While there was evidence of learning across the trials, these results suggest that moderate hypohydration did not affect isokinetic muscular strength and endurance, and support others who have suggested similar results for other measures of muscular performance.

Distribution of Muscle Mass and Maximal Exercise Performance in Patients With COPD

To investigate the distribution of reduction in lean body mass (LBM) and whether LBM in legs (LBMlegs) can be a determinant of maximal exercise performance in COPD patients. Thirty-eight male outpatients with COPD (mean +/- SD FEV1, 47.4 +/- 24.0% of predicted) who underwent complete pulmonary function testing were classified into two groups according to FEV1 expressed as a percentage of predicted value. Group A comprised 21 patients with mild-to-moderate airflow limitation (FEV(1) > or =35% predicted), and group B comprised 17 patients with severe airflow limitation (FEV1 < 35% predicted). LBM, which represents skeletal muscle mass, was measured by dual energy x-ray absorptiometry (DXA) and was assessed separately in arms, legs, and trunk. Maximal oxygen uptake VO2max was measured during maximal exercise on a cycle ergometer. LBM in each region was expressed as a percentage of ideal body weight (IBW). LBM in arms (LBMarms)/IBW, LBMlegs/IBW, and LBM in trunk (LBMtrunk)/IBW were significantly depleted in group B compared with group A (p < 0.01). LBMlegs expressed as a percentage of total LBM (LBMlegs/total LBM) was significantly lower in group B (p < 0.05), although there was no significant difference in LBMarms/total LBM and LBMtrunk/total LBM between the two groups. VO2max correlated significantly with LBMlegs/IBW in group A, but not in group B. By stepwise regression analysis, LBMlegs/IBW appeared to be a significant predictor of VO2max in group A, while not in group B. LBMlegs was a significant predictor of maximal exercise performance in patients with mild-to-moderate airflow limitation, but not in patients with severe airflow limitation who had disproportional reduction in LBMlegs.

Route-Dependent Endocrine and Metabolic Effects of Estrogen Replacement Therapy

The route of estrogen replacement therapy has a major impact on the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis. Estrogen administration by the oral, but not the transdermal, route reduces IGF-I and increases GH levels in postmenopausal women. This perturbation of the GH-IGF-I axis occurs with different forms of estrogen treatment, indicating that the dissociation of the somatotropic axis and concomitant increase in GH-binding protein levels are intrinsic effects of the oral route of estrogen administration. In clinical studies, oral estrogen reduced postprandial lipid oxidation, compared with transdermal estrogen. Oral estrogen was also associated with a reduction in lean body mass and an increase in fat mass, compared with transdermal estrogen. In contrast, the route of estrogen therapy had no impact on carbohydrate metabolism or the estrogen-induced increase in bone mineral density. The findings of route-dependent changes in body composition add a new dimension to health considerations concerning estrogen therapy in postmenopausal women and may have significant implications for estrogen replacement therapy in young hypogonadal females.

Metabolic compensation during high energy output in fasting, lactating grey seals (Halichoerus grypus): metabolic ceilings revisited

Lactation is the most energetically expensive period for female mammals and is associated with some of the highest sustained metabolic rates (SusMR) in vertebrates (reported as total energy throughput). Females typically deal with this energy demand by increasing food intake and the structure of the alimentary tract may act as the central constraint to ceilings on SusMR at about seven times resting or standard metabolic rate (SMR). However, demands of lactation may also be met by using a form of metabolic compensation such as reducing locomotor activities or entering torpor. In some phocid seals, cetaceans and bears, females fast throughout lactation and thus cannot offset the high energetic costs of lactation through increased food intake. We demonstrate that fasting grey seal females sustain, for several weeks, one of the highest total daily energy expenditures (DEE; 7.4 x SMR) reported in mammals, while progressively reducing maintenance metabolic expenditures during lactation through means not explained by reduction in lean body mass or behavioural changes. Simultaneously, the energy-exported in milk is progressively increased, associated with increased lipoprotein lipase activity in the mammary gland, resulting in greater offspring growth. Our results suggest that females use compensatory mechanisms to help meet the extraordinary energetic costs of lactation. Additionally, although the concepts of SusMR and ceilings on total DEE may be somewhat different in fasting lactating species, our data on phocid seals demonstrate that metabolic ceilings on milk energy output, in general, are not constrained by the same kind of peripheral limitations as are other energy-consuming tissues. In phocid seals, the high ceilings on DEE during lactation, coupled with metabolic compensation, are undoubtedly important factors enabling shortened lactation.

Body composition and muscle constituents during weight loss: studies in obese patients following gastroplasty.

The influence of rapid and prolonged weight loss on body composition and muscle constituents in the obese patient is not well known. There are serious complications related to rapid and prolonged weight loss. It is of general interest to increase the understanding of the mechanisms and consequences of significant weight loss in man. In 40 obese patients, the body composition and muscle constituents were studied before and during 1 year of weight loss following gastroplasty. The study was undertaken in two groups (A and B) of obese patients, comprising 32 women and eight men, body weight 82-175 kg and aged 24-49 years. Mean BMI in group A and B was 45 (W/H(2)) and 43 (W/H(2)) respectively. Body composition was assessed by total body potassium measurements and muscle constituents were determined by analyses of muscle specimens obtained percutaneously. The preoperative body composition was found to be equal parts of lean body mass and body fat. Preoperatively, muscle constituents revealed a higher protein content per cell and a lower potassium concentration related to fat-free solids. The loss of 18-28% body fat and lean body mass occurred in equal proportions during the first 3 postoperative months of rapid weight loss, followed by a continuous decrease of body fat but not of lean body mass. The concentrations of proteins and potassium per muscle cell revealed a reduction during the period of rapid weight loss. The RNA/DNA ratio 1 year after surgery was still reduced, indicating a low protein synthesis rate. Preoperatively mean body fat accounted for 50% of the body weight in obese patients. Following weight loss, body fat, lean body mass and concentrations of proteins were reduced compared to preoperative values. After the period of rapid weight loss, with reduction of lean body mass and body fat in parallel, a progressive reduction of body fat was observed whereas the lean body mass did not decrease further. Protein synthesis rate was still low 12 months after surgery.

Effects of growth hormone on body composition and bone metabolism.

Physiologic effects of growth hormone (GH) extend beyond the stimulation of linear growth during childhood and adolescence. These effects include building and sustaining lean body mass, facilitating the utilization of fat mass for energy needs, and maintaining bone mineral density. These nongrowth effects of GH appear to be important throughout life. Children and adults with severe GHD demonstrate marked reductions in lean body mass, increases in percent body fat, and subnormal bone mineral density. Replacement of GH attenuates these abnormalities, though it remains unknown whether it does so completely. Children with body composition abnormalities resembling the GHD state (e.g., Prader-Willi syndrome) also appear to respond favorably to administration of GH treatment, and demonstrate concomitant improvements in strength and agility. Long-term body composition benefits of GH supplementation in these and other non-GHD individuals remain unproven.

A study on how a 6-month aerobic exercise program can modify coronary risk factors depending on their severity in middle-aged sedentary women

It is well known that physical exercise can reduce coronary risk factors. But how an aerobic exercise modifies coronary risk factors in relation to severity and physical fitness is still controversial.Fifty-four middle-aged women (mean age, 55 years) completed a 6-month on-site and home-based anaerobic threshold-level exercise program. The changes in coronary risk factor profiles were observed during the pre-intervention and intervention periods. Before the intervention (during control period), most coronary risk factors showed a rather unfavorable trend. After the program, their mean body weight decreased from 56.7 to 55.7 kg (p>0.05) and the proportion of body fat from 30.9 to 27.9% (p>0.05) without any reduction in lean body mass. Systolic blood pressure (SBP) decreased from 129.0 to 125.0 mm Hg (p>0.05) and diastolic blood pressure from 79.5 to 76.6 mm Hg (p>0.05). Fasting plasma glucose (FPG) declined from 109.6 to 103.4 mg/dl (p>0.05). Changes in SBP and FPG were most remarkable in their respective worst tertile. Serum lipids improved only modestly. Maximum oxygen uptake increased from 23.6 to 26.1 ml/kg/min (p>0.01). However, no significant correlations were found between changes in coronary risk factors and those in physical fitness. We conclude that the 6-month aerobic exercise program would modify women's coronary risk factors depending on their initial values, probably independently of the changes in physical fitness.

Inhibition of muscle protein synthesis by alcohol is associated with modulation of eIF2B and eIF4E.

The present study examined potential mechanisms for the inhibition of protein synthesis in skeletal muscle after chronic alcohol consumption. Rats were maintained on an alcohol-containing diet for 14 wk; control animals were pair fed. Alcohol-induced myopathy was confirmed by a reduction in lean body mass as well as a decrease in the weight of the gastrocnemius and psoas muscles normalized for tibial length. No alcohol-induced decrease in total RNA content (an estimate of ribosomal RNA) was detected in any muscle examined, suggesting that alcohol reduced translational efficiency but not the capacity for protein synthesis. To identify mechanisms responsible for regulating translational efficiency, we analyzed several eukaryotic initiation factors (eIF). There was no difference in the muscle content of either total eIF2alpha or the amount of eIF2alpha in the phosphorylated form between alcohol-fed and control rats. Similarly, the relative amount of eIF2Bepsilon in muscle was also not different. In contrast, alcohol decreased eIF2B activity in psoas (fast-twitch) but not in soleus or heart (slow-twitch) muscles. Alcohol feeding also dramatically influenced the distribution of eIF4E in the gastrocnemius (fast-twitch) muscle. Compared with control values, muscle from alcohol-fed rats demonstrated 1) an increased binding of the translational repressor 4E-binding protein 1 (4E-BP1) with eIF4E, 2) a decrease in the phosphorylated gamma-form of 4E-BP1, and 3) a decrease in eIF4G associated with eIF4E. In summary, these data suggest that chronic alcohol consumption impairs translation initiation in muscle by altering multiple regulatory sites, including eIF2B activity and eIF4E availability.

Resting energy expenditure in reduced-obese subjects in the National Weight Control Registry

Weight loss in obese subjects is associated with a reduction in resting metabolic rate (RMR). Whether the reduction can be explained solely by a reduction in lean body mass remains controversial. Our objective was to determine whether the reduction in RMR after weight loss was proportional to the decrease in lean mass alone or was greater than could be explained by body composition. We measured the RMR, fasting respiratory quotient (RQ), and body composition in 40 reduced-obese subjects [ie, 7 men and 33 women who had lost > or = 13.6 kg (30 lb) and maintained the loss for > or = 1 y] enrolled in the National Weight Control Registry and 46 weight-matched control subjects (9 men, 37 women). A stepwise multiple regression found lean mass, fat mass, age, and sex to be the best predictors of RMR in both groups. After adjusting RMR for these variables, we found no significant difference in RMR (5926 +/- 106 and 6015 +/- 104 kJ/d) between the 2 groups (P = 0.35). When we adjusted fasting RQ for percentage body fat and age, the reduced-obese group had a slightly higher (0.807 +/- 0.006) RQ than the control group (0.791 +/- 0.005, P = 0.05). This may have been due to the consumption of a diet lower in fat or to a reduced capacity for fat oxidation in the reduced-obese group. These results show that in at least some reduced-obese individuals there does not seem to be a permanent obligatory reduction in RMR beyond the expected reduction for a reduced lean mass.

ABSOLUTE PEAK OXYGEN UPTAKE IS A BETTER INDICATOR OF IMPROVED EXERCISE CAPACITY IN PATIENTS FOLLOWING CARDIAC TRANSPLANTATION

1719 Exercise capacity remains subnormal in heart transplant recipients (HTR) and is usually expressed as a weight adjusted value. However, body weight usually increases in HTR due to both chronic deconditioning and prednisone therapy-induced reductions in lean body mass. In order to determine the importance of changes in body weight as a contributor to the value of peak oxygen uptake (VO2) expressed as ml/kg/min, we reviewed the records of patients who had measurements of exercise capacity before and after cardiac transplantation. Twenty HTR (age 53.1±10 years) performed a symptom-limited exercise test with respiratory gas analysis on a cycle ergometer ramp protocol before (117±85 days) and following (1972±1189 days) cardiac transplantation. Pre-transplant (Pre-TX) and post-transplant (Post-TX) absolute VO2 (ml/min), weight adjusted VO2 (ml/kg/min), and body weight (kg) mean ± SD values are shown in the table below:TableIncrease in peak VO2 following cardiac transplantation was less when considered weight adjusted (21.2%), than when considered in absolute terms (37.1%). Of five HTR that decreased their exercise capacities following transplantation when judged by weight adjusted values (mean −2.26 ml/kg/min), two of these actually increased their exercise capacities when considered in absolute values (mean +80.7 ml/min). These findings suggest that increases in body weight following cardiac transplantation make absolute VO2 a better comparison between pre- and posttransplant peak VO2 than weight adjusted VO2.

The vitamin status and its adequacy in the elderly: an international overview.

Age-related changes in nutrition can affect the nutritional status of the elderly in a number of ways. Food intake is affected by socio-economic, physiological and pathological factors. The major physiological age-related change is the decrease in the energy requirement due to a reduction in lean body mass and a reduction in physical activity leading to a compensatory decrease in macro- and micronutrient intake of approximately 30% by the age of 80 years. Morbidity and some types of medication, smoking and alcohol consumption also affect the absorption and metabolism of vitamins. The plasma levels of fat-soluble vitamins and carotenoids tend to increase with age with the exception of vitamin D, while certain water-soluble vitamin levels decrease, particularly vitamin B6 and vitamin B12. Many epidemiological studies have examined the vitamin intake and the plasma concentrations of large elderly populations in many regions of the world, but few have specifically determined the incidence of vitamin deficiencies. The criteria for defining deficiency varies between studies making it difficult to compare data from different studies. In the SENECA Study on European elderly evidence for biochemical vitamin deficiency was found in 47% for vitamin D, 23.3% for vitamin B6, 2.7% for vitamin B12 and 1.1% for vitamin E.