Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3β/4E-BP1, and muscle atrophy, including TNFα/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 ± 0.2 years) and 16 older (70 ± 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40–45% in the type II muscle fibers. TNFα and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3β were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNFα, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation.

The effect of training in reduced energy density eating and food self-monitoring accuracy on weight loss maintenance

Background:
Failure to maintain weight losses in lifestyle change programs continues to be a major problem and warrants investigation of innovative approaches to weight control.
Objective:
The goal of this study was to compare two novel group interventions, both aimed at improving weight loss maintenance, with a control group.
Methods and Procedures:
A total of 103 women lost weight on a meal replacement–supplemented diet and were then randomized to one of three conditions for the 14-week maintenance phase: cognitive-behavioral treatment (CBT); CBT with an enhanced food monitoring accuracy (EFMA) program; or these two interventions plus a reduced energy density eating (REDE) program. Assessments were conducted periodically through an 18-month postintervention. Outcome measures included weight and self-reported dietary intake. Data were analyzed using completers only as well as baseline-carried-forward imputation.
Results:
Participants lost an average of 7.6 plusminus 2.6 kg during the weight loss phase and 1.8 plusminus 2.3 kg during the maintenance phase. Results do not suggest that the EFMA intervention was successful in improving food monitoring accuracy. The REDE group decreased the energy density (ED) of their diets more so than the other two groups. However, neither the REDE nor the EFMA condition showed any advantage in weight loss maintenance. All groups regained weight between 6- and 18-month follow-ups.
Discussion:
Although no incremental weight maintenance benefit was observed in the EFMA or EFMA + REDE groups, the improvement in the ED of the REDE group's diet, if shown to be sustainable in future studies, could have weight maintenance benefits.

Association of reduced riparian vegetation cover in agricultural landscapes with coarse detritus dynamics in lowland streams

Studies were conducted on streams flowing through agricultural floodplains in south-eastern Australia to quantify whether reductions in riparian canopy cover were associated with alterations to the input and benthic standing stocks of coarse allochthonous detritus. Comparisons were made among three farmland reaches and three reaches within reserves with intact cover of remnant overstorey trees. Detritus inputs to these reaches were measured monthly over 2 years using litter traps. Direct inputs to streams within the reserves were relatively high (550–617 g ash free dry weight (AFDW) m^–2 year^–1), but were lower at farmland reaches with the lowest canopy covers (83–117 gAFDW m^–2 year^–1). Only a minor fraction of the total allochthonous input (<10%) entered any of the study reaches laterally. The mean amounts of benthic detritus were lowest in the most open farmland reaches. Standing stocks of benthic detritus were found to be highly patchy across a large number of agricultural streams, but were consistently very low where the streamside canopy cover was below ~35%. Canopy cover should be restored along cleared agricultural streams because allochthonous detritus is a major source of food and habitat for aquatic ecosystems. Given the absence of pristine lowland streams in south-eastern Australia, those reaches with the most intact remnant overstorey canopies should be used to guide restoration.

Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance

In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE^-/-) and compared with wild-type littermates. Compared with wild-type littermates, ACE^-/- mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE^-/- mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE^-/- mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excrete in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE^-/- mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.

Television viewing and abdominal obesity in young adults : is the association mediated by food and beverage consumption during viewing time or reduced leisure-time physical activity?

BACKGROUND:The behavioral pathways through which television (TV) viewing leads to increased adiposity in adults are unclear.

OBJECTIVE:We wanted to determine whether the association between TV viewing and abdominal obesity in young adults is mediated by food and beverage consumption during TV viewing time or by a reduction in overall leisure-time physical activity (LTPA).

DESIGN:This study involved a cross-sectional analysis of data from 2001 Australian adults aged 26–36 y. Waist circumference (WC) was measured at study clinics, and TV viewing time, frequency of food and beverage consumption during TV viewing, LTPA, and demographic characteristics were self-reported.

RESULTS:Women watching TV >3 h/d had a higher prevalence of severe abdominal obesity (WC: =88 cm) compared with women watching =1 h/d [prevalence ratio (PR): 1.89; 95% CI: 1.32, 2.71]. Moderate abdominal obesity (WC: 94–101.9 cm) was more prevalent in men watching TV >3 h/d than in men watching =1 h/d (PR: 2.16; 95% CI: 1.37, 3.41). Adjustment for LTPA made little difference, but adjustment for food and beverage consumption during TV viewing attenuated the associations (PR: 1.48; 95% CI: 1.01, 2.17 for women; PR: 1.73; 95% CI: 1.06, 2.83 for men).

CONCLUSIONS:The association between TV viewing and WC in young adults may be partially explained by food and beverage consumption during TV viewing but was not explained by a reduction in overall LTPA. Other behaviors likely contribute to the association between TV viewing and obesity.

Reduced egg investment can conceal helper effects in cooperatively breeding birds

Cooperative breeding systems are characterized by nonbreeding helpers that assist breeders in offspring care. However, the benefits to offspring of being fed by parents and helpers in cooperatively breeding birds can be difficult to detect. We offer experimental evidence that helper effects can be obscured by an undocumented maternal tactic. In superb fairy-wrens (Malurus cyaneus), mothers breeding in the presence of helpers lay smaller eggs of lower nutritional content that produce lighter chicks, as compared with those laying eggs in the absence of helpers. Helpers compensate fully for such reductions in investment and allow mothers to benefit through increased survival to the next breeding season. We suggest that failure to consider maternal egg-investment strategies can lead to underestimation of the force of selection acting on helping in avian cooperative breeders.

Probing the flexibility of the DsbA oxidoreductase from Vibrio cholerae - a 15N -1H heteronuclear NMR relaxation analysis of oxidised and reduced forms of DsbA

We have determined the structure of the reduced form of the DsbA oxidoreductase from Vibrio cholerae. The reduced structure shows a high level of similarity to the crystal structure of the oxidized form and is typical of this class of enzyme containing a thioredoxin domain with an inserted α-helical domain. Proteolytic and thermal stability measurements show that the reduced form of DsbA is considerably more stable than the oxidized form. NMR relaxation data have been collected and analyzed using a model-free approach to probe the dynamics of the reduced and oxidized states of DsbA. Akaike's information criteria have been applied both in the selection of the model-free models and the diffusion tensors that describe the global motions of each redox form. Analysis of the dynamics reveals that the oxidized protein shows increased disorder on the pico- to nanosecond and micro- to millisecond timescale. Many significant changes in dynamics are located either close to the active site or at the insertion points between the domains. In addition, analysis of the diffusion data shows there is a clear difference in the degree of interdomain movement between oxidized and reduced DsbA with the oxidized form being the more rigid. Principal components analysis has been employed to indicate possible concerted movements in the DsbA structure, which suggests that the modeled interdomain motions affect the catalytic cleft of the enzyme. Taken together, these data provide compelling evidence of a role for dynamics in the catalytic cycle of DsbA.

Reduced glycogen availability is associated with increased AMPKα2 activity, nuclear AMPKα2 protein abundance, and GLUT4 mRNA expression in contracting human skeletal muscle

Glycogen availability can influence glucose transporter 4 (GLUT4) expression in skeletal muscle through unknown mechanisms. The multisubstrate enzyme AMP-activated protein kinase (AMPK) has also been shown to play an important role in the regulation of GLUT4 expression in skeletal muscle. During contraction, AMPK [alpha]2 translocates to the nucleus and the activity of this AMPK isoform is enhanced when skeletal muscle glycogen is low. In this study, we investigated if decreased pre-exercise muscle glycogen levels and increased AMPK [alpha]2 activity reduced the association of AMPK with glycogen and increased AMPK [alpha]2 translocation to the nucleus and GLUT4 mRNA expression following exercise. Seven males performed 60 min of exercise at ~70% [VO.sub.2] peak on 2 occasions: either with normal (control) or low (LG) carbohydrate pre-exercise muscle glycogen content. Muscle samples were obtained by needle biopsy before and after exercise. Low muscle glycogen was associated with elevated AMPK [alpha]2 activity and acetyl-CoA carboxylase [beta] phosphorylation, increased translocation of AMPK [alpha]2 to the nucleus, and increased GLUT4 mRNA. Transfection of primary human myotubes with a constitutively active AMPK adenovirus also stimulated GLUT4 mRNA, providing direct evidence of a role of AMPK in regulating GLUT4 expression. We suggest that increased activation of AMPK [alpha]2 under conditions of low muscle glycogen enhances AMPK [alpha]2 nuclear translocation and increases GLUT4 mRNA expression in response to exercise in human skeletal muscle.

N-Acetylcysteine infusion does not affect glucose disposal during prolonged moderate-intensity exercise in humans

There is evidence that reactive oxygen species (ROS) signalling is required for normal increases in glucose uptake during contraction of isolated mouse skeletal muscle, and that AMP-activated protein kinase (AMPK) is involved. The aim of this study was to determine whether ROS signalling is involved in the regulation of glucose disposal and AMPK activation during moderate-intensity exercise in humans. Nine healthy males completed 80 min of cycle ergometry at 62 ± 1 of peak oxygen consumption ( . A 6,6-2H-glucose tracer was infused at rest and during exercise, and in a double-blind randomised cross-over design, N-acetylcysteine (NAC) or saline (CON) was co-infused. NAC was infused at 125 mg kg?1h?1for 15 min and then at 25 mg kg?1h?1for 20 min before and throughout exercise. NAC infusion elevated plasma NAC and cysteine, and muscle NAC and cysteine concentrations during exercise. Although neither NAC infusion nor exercise significantly affected muscle reduced or oxidised glutathione (GSH or GSSG) concentration (P> 0.05), S-glutathionylation (an indicator of oxidative stress) of a protein band of ?270 kDa was increased ?3-fold with contraction and this increase was prevented by NAC infusion. Despite this, exercised-induced increases in tracer determined glucose disposal, plasma lactate, plasma non-esterified fatty acids (NEFAs), and decreases in plasma insulin were not affected by NAC infusion. In addition, skeletal muscle AMPK? and acetyl-CoA carboxylase-? (ACC?) phosphorylation increased during exercise by ?3- and ?6-fold (P< 0.05), respectively, and this was not affected by NAC infusion. Unlike findings in mouse muscle ex vivo, NAC does not attenuate skeletal muscle glucose disposal or AMPK activation during moderate-intensity exercise in humans.

Why business academics remain in Australian universities despite deteriorating working conditions and reduced job satisfaction : an intellectual puzzle

In the last two decades, Australia's 38 universities have been subjected to profound changes affecting the working lives of their academic staff. That the working conditions of staff have deteriorated cannot be denied, while many studies have shown that job satisfaction has been affected adversely. Paradoxically, there is little evidence that academics are seeking employment outside the university system. In this article, the authors report the findings from their survey of over 3000 academics employed in business disciplines in Australian universities, which aimed to find explanations for this phenomenon.

Comparison of aspirin and indomethacin pre-treatments on the responses to reduced renal artery pressure in conscious dogs

To examine the role of prostaglandins in physiologically induced renin release, we reduced renal artery pressure within the autoregulatory range in chronically instrumented conscious dogs with aspirin, indomethacin or no pre-treatment. In untreated dogs, reduction of renal artery pressure to 60 mmHg for 90 min produced rises in plasma renin activity (+ 5.4 +/- 1.0 ng ml.-1 hr-1) and mean arterial pressure (+ 17 +/- 2 mmHg) without significant effect on renal blood flow (n = 13). Aspirin pre-treatment (2 X 25-40 mg kg-1 orally) had no effect on the renin, arterial pressure or renal blood flow responses to renal artery pressure reduction (n = 7). In contrast, indomethacin pre-treatment (2 X 2-3 mg kg-1 orally) significantly lessened the increase in plasma renin activity during reduced renal artery pressure (+ 2.0 +/- 0.3 ng ml.-1 hr-1, n = 11). The relative effectiveness of aspirin and indomethacin in inhibiting prostaglandin production in the kidney was then tested in separate experiments by measuring the renal blood flow responses to renal artery injections of arachidonate (5-200 micrograms kg-1). In the doses used above, aspirin markedly attenuated the blood flow response to arachidonate but indomethacin had almost no effect. Both aspirin and indomethacin abolished the hypotensive effect of intravenous arachidonate (0.5 mg kg-1). These results tentatively suggest that indomethacin may not effectively inhibit renal prostaglandin production in conscious dogs at the doses used in these experiments. Thus the reduced renin release in response to lowered renal artery pressure in indomethacin pre-treated dogs may have been due to another, non-prostaglandin action of indomethacin. The results from the aspirin pre-treated dogs suggest that prostaglandins are not involved in the release of renin in response to reduced renal artery pressure in conscious dogs.