Familial dependence of the resting metabolic rate

Human obesity is known to be a familial disorder. We studied 130 nondiabetic adult southwestern American Indians (74 men and 56 women) from 54 families to determine whether the resting metabolic rate, as measured by indirect calorimetry, is a familial trait that is independent of individual differences in fat-free mass (estimated mass of metabolically active tissue), age, and sex. We found that most of the variance in the resting metabolic rate (83 percent, P less than 0.0001) was accounted for by three covariates--fat-free mass, age, and sex--and that fat-free mass was the most important determinant. Family membership accounted for an additional 11 percent (P less than 0.0001) of the variance in the resting metabolic rate. Thus, resting metabolic rate is a familial trait in this population, and it is independent of differences in fat-free mass, age, and sex. We also found that persons from families with lower resting metabolic rates were no more obese than persons from families with higher metabolic rates. This finding may be partly explained by the close correlation between fat-free mass and percentage of body fat (r = 0.81, P less than 0.0001), which indicates that the resting metabolic rate, as adjusted for fat-free mass, is already partly adjusted for obesity. Only prospective studies will elucidate whether the familial dependence of the resting metabolic rate is a contributing mechanism to the familial predisposition to obesity.     

The effects of a single bout of exercise on resting energy expenditure and respiratory exchange ratio

We investigated the effects of a single bout of aerobic and resistance exercise of similar relative intensity and duration on resting energy expenditure (REE) and substrate utilisation. Ten young healthy males volunteered [age 22 (1.8) years, weight 76 (7.9) kg, height 176 (4.1) cm, percentage body fat 10.5 (4.0)%; mean (SEM)]. They randomly underwent three conditions in which they either lifted weights for 60 min at 70–75% of 1-RM (WL), ran for 60 min at 70–75% of maximal oxygen intake (R) or did not exercise (C). REE and substrate utilisation, determined via respiratory exchange ratio (R), were measured prior to exercise, and 10, 24, 48 and 72 h post-exercise. It was revealed that REE was significantly elevated (P<0.05) 10 and 24 h after the end of WL [2,124 (78) and 2,081 (76) kcal, respectively] compared to pre-exercise [1,972 (82) kcal]. REE was also significantly increased (P<0.05) 10 and 48 h after the completion of R [2,150 (73) and 1,995 (74) kcal, respectively] compared to pre-exercise data [1,862 (70) kcal]. R was lower 10 and 24 h following either WL or R [0.813 (0.043); 0.843 (0.040) and 0.818 (0.021); 0.832 (0.021), respectively] compared to baseline measurements [0.870 (0.025) and 0.876 (0.04), respectively]. Creatine kinase was significantly elevated (P<0.05) 24 h after both WL and R, whereas delayed onset muscle soreness became significantly elevated (P<0.05) 24 h after only WL. There were no significant changes for any treatment in thyroid hormones (T₃ and T₄). These results suggest that a single bout of either WL or R exercise, characterised by the same relative intensity and duration, increase REE and fat oxidation for at least 24 h post-exercise.     

An isopropanolic extract of black cohosh does not increase mammographic breast density or breast cell proliferation in postmenopausal women

OBJECTIVE: The aim of this study was to determine the effects of the isopropanolic extract of black cohosh (Remifemin) on mammographic breast density and breast epithelial proliferation in healthy, naturally postmenopausal women with climacteric symptoms. DESIGN: This was a prospective, open, uncontrolled drug safety study in which baseline status was compared with status after 6 months of treatment by blinded observers. A total of 74 women were treated with 40 mg black cohosh daily, and 65 women completed the study. Mammograms were performed, and breast cells were collected by percutaneous fine needle aspiration biopsies at baseline and after 6 months. Mammographic density was quantified according to the Wolfe classification or a percentage scale. Breast cell proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody. Safety was monitored by adverse event reporting, laboratory assessments, and measurement of the endometrium by vaginal ultrasound. RESULTS: None of the women showed any increase in mammographic breast density. Furthermore, there was no increase in breast cell proliferation. The mean change +/- SD in proportion of Ki-67-positive cells was -0.5% +/- 2.4% (median, 0.0; 95% CI = -1.32 to 0.34) for paired samples. The mean change in endometrial thickness +/- SD was 0.0 +/- 0.9 mm (median, 0.0). A modest number of adverse events were possibly related to treatment, but none of these were serious. Laboratory findings and vital signs were normal. CONCLUSIONS: The findings suggest that the isopropanolic extract of black cohosh does not cause adverse effects on breast tissue. Furthermore, our data do not indicate to any endometrial or general safety concerns during 6 months of treatment.     

A simplified procedure of direct calorimetry for bedside monitoring of the resting metabolic rate

A simplified procedure of direct calorimetry (SPDC) for determination of resting metabolic rate of respiratory uncompromised subjects in a supine position is presented. This procedure was based on computer-assisted measurements of heat losses due to evaporation, radiation, conduction, and convection. The subject's total loss of mass was recorded hydraulically with a beam scale and afterwards transformed into a digital electric signal. Differences between dry bulb temperature and mean skin temperature were measured by semiconductor thermistors and also transformed into digital signals. With special software an interfaced personal computer assisted in performing SPDC and in calculating heat losses due to evaporation, radiation, and conduction. In a thermoneutral environment,six healthy volunteers were investigated to determine the mean convective heat transfer coefficient (h _c) from the difference in an individual between the metabolic energy transformation (M) measured by indirect calorimetry (IC) and the sum of heat losses by radiation, conduction, and evaporation. The room-specific value of h _c of 2.12 (SD 0.22) W·m^–2·°C^–1 was in good agreement with data in the literature. Compared to the results of M from a second series of IC, the total heat loss (THL) measured by SPDC in a thermoneutral environment was calculated as 100.5 (SD 6.0) %. The THL by SPDC performed three times at 3-h intervals on ten other volunteers revealed a mean difference of 0.22 (SD 1.74) W·m^–2. Thus, SPDC would seem to be a valid and reproducible method under conditions of thermal neutrality.     

Processing sputum specimens in a refrigerated centrifuge does not increase the rate of isolation of Mycobacterium tuberculosis

A total of 1,047 sputum samples from pulmonary tuberculosis patients was collected in cetyl pyridinium chloride-sodium chloride solution. Each sample was divided into two parts and randomly allocated for the isolation of Mycobacterium tuberculosis, with one part to be processed by the standard method and the other by a modified method. In the standard method, the samples were processed by using nonrefrigerated centrifuges, while in the modified method, they were processed by using a refrigerated centrifuge. Fifty-seven samples that yielded contaminants were excluded, and the remaining 990 samples were taken up for analysis. The rates of isolation of M. tuberculosis with the standard and modified methods were 48.6 and 48.1%, respectively, and the difference was not statistically significant (McNemar's test; P > 0.5). However, 51% of the positive cultures were isolated within 2 weeks with the modified method compared to 37% with the standard method (chi-square test; P < 0.001). The results of the study reveal that processing of sputum samples in a refrigerated centrifuge does not improve the rate of isolation but will result in rapid isolation of M. tuberculosis.     

Effects of spinal anesthesia on resting metabolic rate and quadriceps mechanomyography

Previous work by our group has shown by mechanomyography (MMG) that resting muscle is mechanically active. Ten patients having spinal anesthesia for surgery, which paralyses muscle below the waist, were studied to help determine whether resting-muscle mechanical activity plays a significant role in resting metabolism, and to further determine if the phenomenon is neurally mediated. Resting metabolic rate (RMR) by indirect calorimetry, and mid-anterior thigh MMG by accelerometer, were recorded before and during spinal anesthesia. Spinal anesthesia produced a 25% decrease in oxygen uptake (mean ± standard deviation: pre-spinal 228 ± 76; during spinal 171 ± 67 ml min⁻¹; P < 0.001) and 37% decrease in mean absolute MMG signal amplitude (pre-spinal-anesthetic 10.6 ± 3.9; during spinal: 6.7 ± 3.5 mm s⁻²; P < 0.001). Decreased oxygen uptake in individuals correlated with decreased resting-muscle mechanical activity (R = 0.624; P = 0.05). Paralysis of muscle below the waist reduced RMR and resting-muscle mechanical activity.     

Vimentin expression does not assist in predicting survival in ductal carcinoma of the breast

AIMS: To establish the value of vimentin expression in predicting survival in patients with breast cancer. METHODS: Five-year follow-up data were obtained for 68 patients with ductal carcinoma (NOS) of the breast in whom vimentin expression had been studied in fresh frozen and formalin-fixed, paraffin-embedded tissue. The predictive value on survival of tumour size, growth fraction (as assessed using the Ki67 monoclonal antibody), oestrogen receptor status and Bloom and Richardson grade of the primary tumour, and the presence or absence of lymph node metastases in axillary samples, were also studied. RESULTS: Twenty-two patients died of their disease within 5 years of diagnosis. Vimentin expression either on frozen or paraffin sections did not provide a statistically significant prediction of survival. On univariate analysis tumour grade, size and the presence of lymph node metastases provided prognostic information. Only lymph node status was of independent prognostic importance on multivariate analysis. CONCLUSIONS: Whilst these results confirm the value of established prognostic factors, they do not support the use of vimentin expression in either fresh or fixed tissue for the prediction of survival in ductal carcinoma (NOS) of the breast.     

Short-term exercise training does not improve whole-body heat loss when rate of metabolic heat production is considered

We evaluated the effects of an 8-week exercise training program in previously sedentary individuals on whole-body heat balance during exercise at a constant rate of metabolic heat production. Prior to and after 8 weeks of training, ten participants performed 60-min of cycling exercise at a constant rate of heat production (~450 W) followed by 60-min of recovery, at 30°C and 15% relative humidity. Rate of total heat loss was measured directly by whole-body calorimetry, while rate of metabolic heat production was measured simultaneously by indirect calorimetry. Esophageal (T _es), skin blood flow (SkBF) and local sweat rate (LSR) were also measured continuously. The 8-week exercise training program elicited a 10% increase in maximal aerobic capacity (P < 0.001). Furthermore, exercise training reduced (P ≤ 0.05) baseline (37.10 ± 0.28 vs. 36.95 ± 0.24°C) and end-exercise (37.85 ± 0.30 vs. 37.55 ± 0.20°C) values for T _es as well as onset thresholds for LSR (37.23 ± 0.26 vs. 36.96 ± 0.22°C, P < 0.001) and SkBF (37.16 ± 0.38 vs. 36.83 ± 0.26°C, P < 0.001). However, these improvements in thermoregulatory function did not translate into a greater rate of total heat loss between the pre- and post-training exercise trials (P = 0.762). Furthermore, there were no differences in SkBF (P = 0.546) and LSR (P = 0.475) from pre- to post-training. Although physical training resulted in significant improvements of cardiorespiratory and thermoregulatory functions, these adaptations did not improve whole-body and local heat loss responses during exercise performed at a given rate of metabolic heat production.     

Unloading does not increase brown-adipose-tissue activity in rat pups

Our previous study has shown that chronic hindlimb suspension leads to an increase in both the thermogenic capacity and the activity in brown adipose tissue (BAT) of adult rats (Yamashita, H., Ohira, Y., Wakatsuki, T., Yamamoto, M., Kizaki, T., Oh-ishi, S., Sato, Y. and Ohno, H. (1995). J. Appl. Physiol. 78: 384-387). In order to examine if unloading also increases the BAT activity in rat pups, the hindlimbs in the suspended pups were unloaded by tail suspension beginning on postnatal day 4 and suspended until day 21. The thermogenic activity (which was assessed by guanosine 5'-diphosphate binding to BAT mitochondria) was markedly lower in 21-day-old suspended pups than in 21-day-old control pups, although there was no difference in uncoupling protein 1 (UCP1) content or UCP1 mRNA expression in the BAT mitochondrial fraction between both pups. Likewise, there was no disparity in either adrenal or thymus mass between the control and suspended pups throughout the experiment. These results suggest that, in contrast to adult rats, chronic hindlimb suspension leads to a decrease in the thermogenic activity in BAT of rat pups possibly for reason that pups are less susceptible to the stress of unloading.     

Low-dose iron supplementation does not increase HIV-1 load

Observational data suggest that iron may increase HIV replication and the rate of progression of HIV infection. This is worrying, and may impede the international commitment to combat iron deficiency. However, it is crucial to clarify the role of iron in HIV infections, since iron is universally administered to anaemic patients and pregnant women, even in areas with high HIV prevalence. Based on a historical iron trial, we assessed the effect of 60 mg of elemental iron given twice weekly over four month on HIV-1 viral load. There was no effect on viral load, but effects of higher doses of iron cannot be excluded.     

A single bout of torpor in mice protects memory processes

Memory consolidation is the process by which new and labile information is stabilized as long-term memory. Consolidation of spatial memories is thought to involve the transfer of information from the hippocampus to cortical regions. While the hypometabolic and hypothermic state of torpor dramatically changes hippocampal connectivity, little work has considered the functional consequences of these changes. The present study examines the role of a single bout of shallow torpor in the process of memory consolidation in mice. Adult female C57Bl/6NHSD mice were trained on the Morris Water Maze (MWM) task. Immediately following acquisition, the mice were exposed to one of four experimental manipulations for 24 h: fasted at an ambient temperature of 19 °C, fasted at 29 °C, allowed free access to food at 19 °C, or allowed free access to food at 29 °C. Mice fasted at 19 °C entered a bout of torpor as assessed by core body temperature while none of the mice in the other conditions did so. Spatial biases were then assessed with a probe trial in the MWM. During the probe trial, mice that had entered torpor and mice that were fed at 29 °C spent twice as much time in the prior target platform location than mice that were fed at 19 °C and those that were fasted at 29 °C. These findings demonstrate that, while food restriction or cool ambient temperature independently disrupt memory processes, together they cause physiological changes including the induction of a state of torpor that result in functional preservation of the memory process.     

A meta-analysis of the effects of exercise and/or dietary restriction on resting metabolic rate

A meta-analysis was used to examine the independent and interactive effects of dietary restriction, endurance exercise training and gender on resting metabolic rate (RMR). Sixty different group means (covering 650 subjects) were identified from the scientific literature and subjected to meta-analysis techniques. Collectively (i.e., all groups combined), body weight loss was greater (P < 0.05) for men ( 18 kg) than for women ( 12 kg). There were no statistically significant exercise training or gender effects on RMR during weight loss. Collectively (i.e., all groups combined), dietary restriction resulted in a – 0.59 kJ min^–1 ( – 12%) decrease in RMR (P < 0.05). When normalized to body weight, RMR was reduced by less than 2% (P < 0.05). These data suggest that exercise training does not differentially affect RMR during diet-induced weight loss. In addition, decreases in resting metabolism appear to be proportional to the loss of the metabolically active tissue.     

Stretch-induced increase of resting intracellular calcium concentration in single guinea-pig ventricular myocytes.

Single guinea-pig ventricular myocytes were loaded with the fluorescent Ca2+ indicator Indo-1 AM and stretched by carbon fibres. Stretching increased resting tension. Sarcomere lengths were increased by 2-18%. It was observed that a stretch increased resting [Ca2+]i in seven out of eight cells. The change in [Ca2+]i increased with the size of the stretch and returned to pre-stretch levels on return to resting cell length. These observations suggest a means by which changes in resting muscle length can modify the contractile state of cardiac muscle.     

B-cell deficiency suppresses vaccine-induced protection against murine filariasis but does not increase the recovery rate for primary infection

To establish the role of B cells and antibodies in destroying filariae, mice lacking mature B cells and therefore unable to produce antibodies were used. Litomosoides sigmodontis offers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in B-cell-deficient mice (BALB/c muMT mice) and wild-type BALB/c mice in two different in vivo situations, vaccination with irradiated larvae and primary infection. In all cases, mice were challenged with subcutaneous inoculation of 40 infective larvae. Vaccine-induced protection was suppressed in B-cell-deficient mice. In these mice, eosinophils infiltrated the subcutaneous tissue normally during immunization; however, their morphological state did not change following challenge inoculation, whereas in wild-type mice the percentage of degranulated eosinophils was markedly increased. From this, it may be deduced that the eosinophil-antibody-B-cell complex is the effector mechanism of protection in vaccinated mice and that its action is fast and takes place in the subcutaneous tissue. In primary infection, the filarial survival and growth was not modified by the absence of B cells. However, no female worm had uterine microfilariae, nor did any mice develop a patent infection. In these mice, concentrations of type 1 (gamma interferon) and type 2 (interleukin-4 [IL-4], IL-5 and IL-10) cytokines in serum were lower and pleural neutrophils were more numerous. The effects of the muMT mutation therefore differ from those in B1-cell-deficient mice described on the same BALB/c background, which reveal a higher filarial recovery rate and microfilaremia. This outlines B2-cell-dependent mechanisms as favorable to the late maturation of L. sigmodontis.     

Intra-specific variation in resting metabolic rate in MF1 mice is not associated with membrane lipid desaturation in the liver

The 'membrane pacemaker' hypothesis provides a putative mechanistic linkage between variations in energy metabolism, rates of ageing and lifespan across different species. Within species we have found positive associations between longevity and metabolism, which contrast the inter-specific trends. It is of interest to know therefore how levels of lipid desaturation in membranes are linked to variation in metabolism between individuals within species. We explored this problem by extracting membrane fatty acids from the livers of mice that varied in their metabolic rate, in a strain (MF1) where we have previously demonstrated a positive association between metabolism and lifespan. We measured resting metabolic rate (RMR) in 60 mice, each measured on three occasions, and measured their body compositions using dual energy X-ray absorptiometry (DXA). We selected 28 individuals that exhibited a wide variation in their mean resting metabolic rates (RMR) and extracted membrane lipids from the livers of these mice post mortem and analysed them for the patterns of contribution of different fatty acids. We then sought associations between the levels of membrane desaturation and the individual variability in RMR, using the proportional contributions of each fatty acid as predictors in a stepwise regression or by re-describing the variation in fatty acyl lipids using a PCA analysis and then seeking associations between scores on the derived components and RMR. We used whole animal RMRs and also RMR with the effects of body composition (fat free mass) removed. The level of individual variation in RMR was consistent with our previous observations. There was a significant positive association (p=0.019) between the proportion of palmitic acid (16:0) in the membranes and RMR, which was strengthened (p=0.014) when we adjusted RMR for differences in fat free mass. The proportion of palmitic acid (16:0) explained 20.9% of the individual variation in residual RMR. There was no association between RMR or mass adjusted RMR and the proportional representation of any other fatty acid, including 22:6 (DHA) predicted by the membrane pacemaker hypothesis to be of particular significance. High levels of saturated fatty acids in the membranes of mice with high rates of metabolism may contribute to their greater longevity, but the mechanism tying together increased membrane saturation with elevated RMR remains unclear.     

Strenuous prolonged exercise elevates resting metabolic rate and causes reduced mechanical efficiency

Resting O2 consumption, net mechanical efficiency during cycling exercise and excess postexercise O2 consumption (EPOC) was measured in 15 army cadets after 3 or 4 days of continuous simulated combat exercises (estimated energy demand: 40 MJ day-1), no organized sleep and virtually no food intake (stress experiment). They exercised for 30 minutes at a work load corresponding to about 50% of maximal O2 uptake. An identical test using the same absolute work load was repeated when the cadets were completely recovered from the combat course (control experiment). Resting O2 consumption increased by 15% from 279 +/- 7 ml min-1 (control) to 320 +/- 8 ml min-1 (stress, P less than 0.001). Mechanical efficiency decreased from 24.6 +/- 0.4% (control) to 20.9 +/- 0.2% (stress, P less than 0.001). EPOC1h increased from 0.58 +/- 0.41 l (control) to 2.24 +/- 0.2% (stress, P less than 0.05). Glucose infusion during exercise (0.20 g kg-1 body weight) had no effect on mechanical efficiency or EPOC. About 1/5 of the increase in exercise O2 uptake can be explained by a substrate shift from carbohydrates to fat, as evidenced by a reduction in R-value during exercise from 0.90 +/- 0.012 (control) to 0.80 +/- 0.010 (stress). Hence, after severe physical stress combined with sleep deprivation and food restriction, O2 uptake is increased both at rest and during submaximal exercise.     

The impact of high-intensity intermittent exercise on resting metabolic rate in healthy males

Introduction

High-intensity intermittent exercise training (HIT) may favourably alter body composition despite low training volumes and predicted energy expenditure (EE).

Purpose

To characterise the acute impact of two common HIT protocols on EE and post-exercise oxygen consumption (11 h EPOC).

Methods

Oxygen consumption (l min^?1), respiratory exchange ratio (RER) and EE were measured in nine healthy, lean males over 12 h under three conditions: control (CON), HIT1 (10 × 1 min high-intensity cycling bouts followed by 1 min rest) and HIT2 (10 × 4 min high-intensity cycling bouts followed by 2 min rest).

Results

Total exercise period EE during HIT1 (1,151 ± 205 kJ) (mean ± SD) was significantly lower than HIT2 (2,788 ± 322 kJ; p < 0.001). EE within the 60 min after exercise was significantly albeit marginally higher after HIT1 (388 ± 44 kJ; p = 0.02) and HIT2 (389 ± 39 kJ; p = 0.01) compared with CON (329 ± 39 kJ), with no difference between exercise conditions (p = 0.778). RER during this period was significantly lower in HIT1 (0.78 ± 0.06; p = 0.011) and HIT2 (0.76 ± 0.04; p = 0.004) compared with CON (0.87 ± 0.06). During the ‘slow phase’ of EPOC (1.25–9.75 h), there were no significant differences in EE (p = 0.07) or RER (p = 0.173) between trials.

Conclusions

Single HIT sessions notably increases EE during exertion; however, the influence on metabolic rate post-exercise is transient and relatively minor.     

A model of vertebrate resting metabolic rate: balancing energetics and O2 transport in system design

In vertebrates, maximal rates of oxygen consumption (V(O(2),max)) exceed resting rates (V(O(2),rest)) by an average factor of ten. This pattern of factorial scope has led to the hypothesis that V(O(2),rest) and V(O(2),max) are causally linked in vertebrates (aerobic capacity model, Bennett and Ruben, Science 206, 649-654, 1979). We propose an alternate theory that vertebrate resting metabolic rates are regulated at levels to optimize metabolic performance during activity, by reducing cardiovascular response times for O(2) transport. First, we argue that circulatory convection has the potential to be rate-limiting to vertebrate aerobic adjustment. We then show mathematically that incremental changes in convection requirements exhibit a nonlinear dependence on initial values. From this, a cost-benefit model is constructed, using energetics and blood-convection requirements, to predict the optimal fractional allocation to V(O(2),rest) in vertebrates as 11% of V(O(2),max). The implications of our results to vertebrate metabolic design and the evolution of endothermy are discussed.     

Theophylline does not inhibit allergen-induced increase in airway responsiveness to methacholine

Allergen-induced increase in airway hyperresponsiveness can be used as a model of airway inflammation for assessing antiasthma pharmacologic agents. Steroids and cromolyn, but not beta-agonists, inhibit this increase; theophylline, recently suggested as having anti-inflammatory effects, has not been evaluated in this model. Six atopic subjects with asthma and with late asthmatic responses (N = 5) and postallergen reduction in a provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) (N = 6) were studied. Sustained-release theophylline (Theo-Dur; Astra Pharmaceuticals Canada, Ltd., Mississauga, Canada), 300 mg, and placebo were administered single-blind twice daily for eight doses up to 1 hour before allergen inhalation; cromolyn sodium, 10 mg, was administered in a single dose 10 minutes before allergen inhalation on another day as a "positive control." Mean theophylline levels were in the low therapeutic range, 57 +/- 17 and 58 +/- 13 mumol/L 1 and 8 hours after the last tablet. The FEV1 was 7% and 9% greater after the seventh and eighth doses of theophylline versus placebo (p less than 0.05). Theophylline also produced a significant (p less than 0.05) twofold increase in methacholine PC20. There was a 40% (p = 0.06) reduction in early asthmatic fall in FEV1 and a 25% (not significant) reduction in late FEV1 fall when theophylline was compared to placebo. Theophylline did not influence the geometric mean allergen-induced fall in methacholine PC20 delta log PC20; this was true individually in five of the six subjects. By contrast, cromolyn sodium inhibited all aspects of the allergen response completely.(ABSTRACT TRUNCATED AT 250 WORDS)