Reduction In Resting Metabolic Rate Research Articles

7494 Glycerol Phenylbutyrate Treatment of Two Patients with Monocarboxylate Transporter 8 Deficiency

Abstract Disclosure: A. Zung: None. N. Sonntag: None. U. Schweizer: None. E. Banne: None. D. Braun: None. Context: Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Currently, the two thyromimetic agents 3,5-diiodothyropropionic acid (DITPA) and triiodothyroacetic acid (TRIAC) have been evaluated in the treatment of these patients, as they both partially restore intracellular TH action independent of MCT8. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. Objective: We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. Methods: We treated two monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, serum markers of peripheral hyperthyroidism, vital signs, anthropometric measurements and neurocognitive functions by several neurodevelopment validated tests. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In-vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P32[1]L mutation. Results: NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment yielded a dose-dependent decrease in FT3 and an increase in FT4 serum levels. The patients showed an elevation in cholesterol levels in parallel with GPB dose, but sex-hormone binding protein (SHBG), another marker of peripheral hyperthyroidism was not affected. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neuro-cognitive improvement was observed, mainly in hyperreflexia score, slight improvement in gross motor functions and a mild progression in cognitive functions. Serum metabolites of GPB did not exceed the toxic range but elevated liver transaminases restricted the dose intensification of GPB. Conclusions: In the first report of GPB treatment in MCT8 deficiency patients we found an improvement in TH profile and body-mass index (BMI). The reduction in T3 levels could contribute to the remarkable increase in BMI-SDS, since various aspects of peripheral hyperthyroidism in MCT8 deficiency, including poor weight gain, were attributed to elevated T3. The limited effects of GPB treatment on cognitive and motor functions can derive from the advanced age of the patients at the time of the intervention. Presentation: 6/2/2024

Randomized Control Study to Evaluate the Effect of Rajyoga Meditation on Metabolic and Psychological Correlates of Health in Patients of Surgical Repair for Congenital Heart Disease

Objectives: Congenital heart diseases (CHDs) and their operative management are a source of emotional and financial stress to the patient and family. Rajyoga meditation (RYM) is a specific art and science of meditation that encompasses but is not limited to mind-body medicine theories, inculcation of values in life, and development of life skills for complete physical, mental, and spiritual well-being. The role of RYM has never been studied in CHD patients, especially children. This study aimed to evaluate the efficacy of the RYM program on resting metabolic rate (RMR) and post-hospitalization behavior questionnaire (PHBQ) immediately after the program and after 1 and 3 months. Material and Methods: It was a single-blind, randomized controlled study. Subjects operated for CHD, in the age group of 8–19 years, were included in the study. Subjects in Group A received cardiac rehabilitation and RYM (Experimental group), whereas subjects in Group B received conventional cardiac rehabilitation (Control group). Result: At one-month follow-up, the experimental group showed a 14.18% reduction in RMR compared to baseline, whereas Group B showed 8.96% elevated RMR from baseline. Group A showed a more significant reduction in RMR at one-month follow-up from baseline as compared to group B (P < 0.05). The patients who underwent RYM training had higher PHBQ (−9.0 [−15.6, −2.5], P < 0.05) in comparison to the control group. Conclusion: The result of this study suggests that the inclusion of RYM along with conventionally given cardiac rehabilitation enhanced metabolic resilience with lowered resting metabolism and enhanced recovery post-surgery in children operated on for CHD. There was an improvement in the psychological adjustment and behavior of adolescents.

Resting Metabolic Rate in Indian Adolescents and Youth with Type 1 Diabetes Mellitus: A Case Controlled Study

Abstract Introduction: Energy metabolism in type 1 diabetes (T1D) is known to be different. Resting metabolic rate (RMR) accounts for the largest portion of total energy needs. The objective of our study was to assess resting metabolic rate and its determinants in adolescents and young adults with T1D in comparison with age- and gender-matched healthy controls. Methods: This cross-sectional study included 97 children and young adults (10–19 years) with type 1 diabetes having a disease duration of at least 1 year. For the control population, 95 age- and gender-matched healthy adolescents were enrolled. Clinical examination and biochemical evaluation of parameters pertaining to diabetes and body composition were estimated, and RMR was measured using indirect calorimetry for both cases and controls. Results: Adolescents with T1D were significantly shorter, and had significantly lower calorie intake, higher RMR and volume of oxygen consumed (VO2) as compared to the healthy controls (P < 0.05). RMR adjusted for weight showed a significant positive correlation with lean body mass (LBM) percentage, and energy intake and a negative correlation with disease duration. Those with a T1D duration of less than 5 years demonstrated a significantly higher RMR, lower body fat percentage, higher LBM percentage, carbohydrate and energy intake/kg body weight and higher calculated insulin sensitivity (IS) as compared to those with greater disease duration. Muscle mass percentage and higher energy intake were found to be significant positive predictors and advancing age/diabetes duration was a negative predictor of weight-adjusted RMR (P < 0.05), whereas IS and male gender tended towards significant negative association (P = 0.06). Conclusion: Indian children with type 1 diabetes had a higher resting metabolic rate as compared to healthy children. Muscle mass, energy intake and diabetes duration were observed to be important predictors of RMR in T1D. Reduction in RMR with advancing age/disease duration may predispose to weight gain and subsequent double diabetes in T1D.

Glycerol Phenylbutyrate Treatment of 2 Patients With Monocarboxylate Transporter 8 Deficiency.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. We treated 2 monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, vital signs, anthropometric measurements, and neurocognitive functions. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P321L mutation. The effects of GPB were compared to the effects of DITPA and TRIAC, thyromimetic medications that the patients had received in the past. NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment reduced high T3 and increased low T4 levels. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neurocognitive improvement was observed, in hyperreflexia score and in cognitive functions. Serum metabolites did not exceed the toxic range, but elevated liver transaminases were observed. In the first report of GPB treatment in MCT8 deficiency we found an improvement in TH profile and body mass index, with minor neurodevelopmental changes.

Environmental variation associated with overwintering elicits marked metabolic plasticity in a temperate salmonid, Salvelinus fontinalis.

Poleward winters commonly expose animals, including fish, to frigid temperatures and low food availability. Fishes that remain active over winter must therefore balance trade-offs between conserving energy and maintaining physiological performance in the cold, yet the extent and underlying mechanisms of these trade-offs are not well understood. We investigated the metabolic plasticity of brook char (Salvelinus fontinalis), a temperate salmonid, from the biochemical to whole-animal level in response to cold and food deprivation. Acute cooling (1°Cday-1) from 14°C to 2°C had no effect on food consumption but reduced activity by 77%. We then assessed metabolic performance and demand over 90 days with exposure to warm (8°C) or cold winter (2°C) temperatures while fish were fed or starved. Resting metabolic rate (RMR) decreased substantially during initial cooling from 8°C to 2°C (Q10=4.2-4.5) but brook char exhibited remarkable thermal compensation during acclimation (Q10=1.4-1.6). Conversely, RMR was substantially lower (40-48%) in starved fish, conserving energy. Thus, the absolute magnitude of thermal plasticity may be masked or modified under food restriction. This reduction in RMR was associated with atrophy and decreases in in vivo protein synthesis rates, primarily in non-essential tissues. Remarkably, food deprivation had no effect on maximum oxygen uptake rates and thus aerobic capacity, supporting the notion that metabolic capacity can be decoupled from RMR in certain contexts. Overall, our study highlights the multi-faceted energetic flexibility of Salvelinus spp. that likely contributes to their success in harsh and variable environments and may be emblematic of winter-active fishes more broadly.

Effects of intermittent dieting with break periods on body composition and metabolic adaptation: a systematic review and meta-analysis.

Intermittent dieting incorporated with break periods (INT-B) has recently been promoted as an alternative dietary approach for optimal weight management. This study assessed the effectiveness of INT-B compared with that of conventional continuous energy restriction (CER) for improving body composition and attenuating metabolic adaptation. A systematic search was conducted on 6 databases using all available records until July 2023. The extracted data included the lead author, year of publication, population characteristics, intervention protocols, duration, and adherence. Random-effects meta-analyses were conducted for within-group and between-group comparisons of anthropometric and metabolic outcomes. Subgroup moderator analysis was performed for the types of INT-B, intervention duration, and population characteristics. Of the 1469 records, 12 randomized trials (with 881 participants) were included. Within-group analyses demonstrated significant improvements in body mass, fat mass, body mass index, body fat percentage, and waist circumference following both INT-B and CER, with no significant group differences. However, resting metabolic rate (RMR) was significantly reduced following CER only. The compensatory reduction in RMR was significantly smaller following INT-B compared with CER, suggesting a lesser degree of metabolic adaptation. INT-B had a more significant effect on RMR retention in individuals with overweight/obesity compared with resistance-trained individuals. This review provides up-to-date evidence for INT-B as a viable dietary strategy to improve body composition and attenuate metabolic adaptation. PROSPERO registration no. CRD42023448959.

Tissue losses and metabolic adaptations both contribute to the reduction in resting metabolic rate following weight loss

ObjectiveTo characterize the contributions of the loss of energy-expending tissues and metabolic adaptations to the reduction in resting metabolic rate (RMR) following weight loss.MethodsA secondary analysis was conducted on data from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy study. Changes in RMR, body composition, and metabolic hormones were examined over 12 months of calorie restriction in 109 individuals. The contribution of tissue losses to the decline in RMR was determined by weighing changes in the size of energy-expending tissues and organs (skeletal muscle, adipose tissue, bone, brain, inner organs, residual mass) assessed by dual-energy X-ray absorptiometry with their tissue-specific metabolic rates. Metabolic adaptations were quantified as the remaining reduction in RMR.ResultsRMR was reduced by 101 ± 12 kcal/d as participants lost 7.3 ± 0.2 kg (both p < 0.001). On average, 60% of the total reduction in RMR were explained by energy-expending tissues losses, while 40% were attributed to metabolic adaptations. The loss of skeletal muscle mass (1.0 ± 0.7 kg) was not significantly related to RMR changes (r = 0.14, p = 0.16), whereas adipose tissue losses (7.2 ± 3.0 kg) were positively associated with the reduction in RMR (r = 0.42, p < 0.001) and metabolic adaptations (r = 0.31, p < 0.001). Metabolic adaptations were correlated with declines in leptin (r = 0.27, p < 0.01), triiodothyronine (r = 0.19, p < 0.05), and insulin (r = 0.25, p < 0.05).ConclusionsDuring weight loss, tissue loss and metabolic adaptations both contribute to the reduction in RMR, albeit variably. Contrary to popularly belief, it is not skeletal muscle, but rather adipose tissue losses that seem to drive RMR reductions following weight loss. Future research should target personalized strategies addressing the predominant cause of RMR reduction for weight maintenance.

Influence of fat-free mass and resting metabolic rate on increased food reinforcement after exercise training

PurposeModels of appetite control have been largely based on negative feedback from gut and adipose signaling to central appetite centers. However, contemporary models posit that fat-free mass (FFM) or the energy demand of FFM [i.e., resting metabolic rate (RMR)] may play a primary role in the motivational drive for food intake (i.e., food reinforcement). The relative reinforcing value of food (RRVfood) is associated with energy intake (EI) and increases with an acute energy deficit. Chronic exercise-induced energy deficits lead to alterations in fat mass (FM), FFM, and RMR and provide an opportunity to test whether change in (∆) FM, ∆FFM, ∆usual EI, or ∆RMR are associated with ∆RRVfood.MethodsParticipants (n = 29, BMI = 25–35 kg/m2) engaged in aerobic exercise expending 300 or 600 kcal, 5 days/weeks for 12 weeks. The reinforcing value of food (PMaxfood) was measured via a computer-based operant responding task and RRVfood was calculated as the reinforcing value of food relative to non-eating sedentary behaviors. RMR was determined by indirect calorimetry and body composition by DXA.ResultsPost-training FFM correlated with usual post-training EI (rs = 0.41, p < 0.05), PMaxfood (rs=0.52, p < 0.01), and RMR (rs = 0.85, p < 0.0001). ∆RMR negatively correlated with ∆PMaxfood (rs = − 0.38, p < 0.05) and with ∆RRVfood (rs = − 0.37, p < 0.05). ∆PMaxfood and ∆RRVfood were not associated with ∆FFM (p = 0.71, p = 0.57, respectively).ConclusionsReductions in RMR with weight loss may increase food reinforcement as means of restoring FFM and RMR to pre-weight loss amounts. Limiting reductions in RMR during weight loss may benefit weight maintenance by restricting increases in food reinforcement after weight loss.

Reconsidering the Energy Homeostasis Hypothesis. the Proposed Role of Fat-Free Mass (FFM) and Resting Metabolic Rate (RMR) Driving Increased Energy Intake After Weight Loss (OR09-04-19)

ObjectivesHypotheses of appetite control and food reinforcement are based on gut and adipose peptide signaling to central appetite centers. Contemporary models propose that RMR and FFM changes modify food reinforcement and this may be best observed after weight loss when body mass is purported to be regained until pre-weight loss FFM is restored. Here we assess the associations of change (∆, post-training value minus pre-training value) in food reinforcement with ∆ fat mass (FM), ∆FFM, and ∆RMR after exercise-induced weight loss. MethodsSubjects (n = 29, BMI = 25–35 kg/m2) engaged in a 6-wk aerobic exercise protocol expending either 300 or 600 kcal, 5 d/wk. Relative reinforcement value of food (RRVfood) was measured via a computer-based operant responding task, in which subjects could “earn” access to food or sedentary reinforcers. Schedules of reinforcement for each alternative started at 4 and doubled after every 5 points. Completed schedules were recorded for each alternative (PMaxfood, PMaxsed) and the ratio ((PMaxfood/(PMaxfood + PMaxsed)) determined RRVfood. RMR was determined by indirect calorimetry. FFM was determined by DEXA. Spearman correlation analysis determined correlations between variables at pre and post, and between ∆ scores. A generalized linear mixed model tested the main and interactive effects of ∆FFM and ∆RMR on ∆PMaxfood. ResultsAt baseline, there were no correlations between outcome measures. At post-training, FFM correlated to PMaxfood (P < 0.01, r = 0.52). ∆RMR negatively correlated with ∆PMaxfood (P < 0.01, r = −0.48) and with ∆RRVfood (P < 0.06, r = −0.36). ∆PMaxfood did not associate with ∆FFM (P = 0.71, r = 0.07). ∆RMR predicted (P < 0.05) ∆PMaxfood when controlling for ∆FFM and ∆PMaxfood*∆FFM. ConclusionsFFM correlated with PMaxfood post-training; however, ∆PMaxfood did not correlate to ∆FFM, so, ∆FFM may be necessary, but insufficient to increase PMaxfood after weight loss. ∆RMR inversely predicted ∆PMaxfood when controlling for FFM, suggesting that reductions in RMR with weight loss increases ∆PMaxfood perhaps as a means of restoring pre-weight loss FFM and RMR. This model would predict that limiting reductions in RMR during weight loss could benefit weight loss maintenance by limiting increases in food reinforcement. Funding SourcesUnited States Department of Agriculture, Agricultural Research Service project 3062-51000-51-00D.

Contribution of Changes in Body Composition and Adaptive Thermogenesis to the Decline in Resting Metabolic Rate During Prolonged Calorie‐Restricted Weight Loss

In the United States, 2 out of 3 adults are overweight or obese. To lose weight, individuals engage in a variety of dietary and exercise interventions. Despite successful weight loss initially, weight loss is typically less than expected and most individuals regain weight. Both phenomena have been linked to a reduction in resting metabolic rate (RMR) secondary to weight loss.ObjectiveTo characterize the independent contributions of changes in body composition, the major predictor of RMR, and adaptive thermogenesis to the observed decline in RMR associated with weight loss. We predict that changes in fat‐free mass and adaptive thermogenesis will both contribute to RMR decline.MethodsSecondary data analysis was conducted on a publically available data set from CALERIE (Comprehensive Assessment of Long‐term Effects of Reducing Intake of Energy), a 2‐year observational calorie restriction study. CALERIE data used for the present analysis examined changes in RMR, body composition, and metabolic hormones over 12 months of 25% calorie restriction in 117 non‐obese (BMI between 22–27.9 kg/m2) men and women with complete data. Changes in RMR were compared between quartiles based on loss of body weight, fat‐free mass, and fat mass. Adaptive thermogenesis was quantified as the reduction in RMR that exceeded the reduction in RMR predicted from changes in organ mass, which was assessed by Dual‐energy X‐ray absorptiometry.ResultsAfter 12 months, mean weight loss was 7.9 ± 0.3 kg (−10.9 ± 0.4%, p&lt;0.001 vs. baseline), and RMR declined by 101 ± 11 kcal/d (−6.8 ± 0.8%, p&lt;0.001 vs. baseline). Individuals who lost the most weight (Q1ΔBW) demonstrated a greater RMR decline than individuals who lost the least weight (Q4ΔBW, p&lt;0.01). The change in RMR did not differ between quartiles based on fat free mass loss (p=0.15), but it was positively associated with the amount of fat loss (p=0.03). In addition, participants who lost the greatest amount of fat mass (Q1ΔFM) exhibited a more pronounced adaptive thermogenic effect (−79 ± 19 kcal/d) than participants with the least amount of fat loss (Q4ΔFM; −10 ± 26 kcal/d, p&lt;0.05 vs. Q1ΔFM). Adaptive thermogenesis was correlated with declines in leptin (r=0.27, p&lt;0.01), T3 (r=0.19, p &lt; 0.05), and insulin (r=0.25, p&lt;0.05).ConclusionsDuring weight loss, the loss of fat mass and adaptive thermogenesis appear to be stronger predictors of RMR decline when compared to the loss of fat‐free mass.Support or Funding InformationThis work was funded in part by the University of Nebraska‐Lincoln McNair Scholars Program and the Undergraduate Creative Activities and Research Experience.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Seasonal variation in energy expenditure in a rodent inhabiting a winter-rainfall desert.

Animals that spend more energy than they obtain risk entering allostatic overload, reducing survival and fitness. They are predicted to adjust their daily energy expenditure (DEE) during periods of food scarcity. Adjustments of DEE to changes in food availability have been well-studied in species in temperate zones during winter, but less so in species enduring seasonal droughts. Likely mechanisms regulating DEE involve adjustments of activity and maintenance metabolism. Species that experience seasonal droughts and changes in food availability, like the African striped mouse (Rhabdomys pumilio), are appropriate model organisms to study the regulation of seasonal changes of DEE. We quantified DEE using the 'doubly labelled water' method, measured resting metabolic rate (RMR), and concomitantly determined activity levels using all-day focal observations of 69 free-living striped mice in the cold moist season with high food availability and the hot dry season with low food availability. Striped mice decreased their DEE in the food scarce dry season using multiple mechanisms, especially reductions in RMR, and reduced overall physical activity. This was further facilitated passively by reduced thermoregulatory costs. Our study demonstrates that animals reduce DEE via active and passive mechanisms in food-restricted environments, and highlights that several environmental factors should be considered simultaneously when aiming to understand how animals cope with harsh environments.

Resting metabolic rate of obese patients under very low calorie ketogenic diet

BackgroundThe resting metabolic rate (RMR) decrease, observed after an obesity reduction therapy is a determinant of a short-time weight regain. Thus, the objective of this study was to evaluate changes in RMR, and the associated hormonal alterations in obese patients with a very low-calorie ketogenic (VLCK)-diet induced severe body weight (BW) loss.MethodFrom 20 obese patients who lost 20.2 kg of BW after a 4-months VLCK-diet, blood samples and body composition analysis, determined by DXA and MF-Bioimpedance, and RMR by indirect calorimetry, were obtained on four subsequent visits: visit C-1, basal, initial fat mass (FM) and free fat mass (FFM); visit C-2, − 7.2 kg in FM, − 4.3 kg in FFM, maximal ketosis; visit C-3, − 14.4 kg FM, − 4.5 kg FFM, low ketosis; visit C-4, − 16.5 kg FM, − 3.8 kg FFM, no ketosis. Each subject acted as his own control.ResultsDespite the large BW reduction, measured RMR varied from basal visit C-1 to visit C-2, − 1.0%; visit C-3, − 2.4% and visit C-4, − 8.0%, without statistical significance. No metabolic adaptation was observed. The absent reduction in RMR was not due to increased sympathetic tone, as thyroid hormones, catecholamines, and leptin were reduced at any visit from baseline. Under regression analysis FFM, adjusted by levels of ketonic bodies, was the only predictor of the RMR changes (R2 = 0.36; p < 0.001).ConclusionThe rapid and sustained weight and FM loss induced by VLCK-diet in obese subjects did not induce the expected reduction in RMR, probably due to the preservation of lean mass.Trial registrationThis is a follow up study on a published clinical trial.

New approaches to determine fatigue in elite athletes during intensified training: Resting metabolic rate and pacing profile.

BackgroundElite rowers complete a high volume of training across a number of modalities to prepare for competition, including periods of intensified load, which may lead to fatigue and short-term performance decrements. As yet, the influence of substantial fatigue on resting metabolic rate (RMR) and exercise regulation (pacing), and their subsequent utility as monitoring parameters, has not been explicitly investigated in elite endurance athletes.MethodTen National-level rowers completed a four-week period of intensified training. RMR, body composition and energy intake were assessed PRE and POST the four-week period using indirect calorimetry, Dual-Energy X-Ray Densitometry (DXA), and three-day food diary, respectively. On-water rowing performance and pacing strategy was evaluated from 5 km time trials. Wellness was assessed weekly using the Multicomponent Training Distress Scale (MTDS).ResultsSignificant decreases in absolute (mean ± SD of difference, p-value: -466 ± 488 kJ.day-1, p = 0.01) and relative RMR (-8.0 ± 8.1 kJ.kg.FFM-1, p = 0.01) were observed. Significant reductions in body mass (-1.6 ± 1.3 kg, p = 0.003) and fat mass (-2.2 ± 1.2 kg, p = 0.0001) were detected, while energy intake was unchanged. On-water 5 km rowing performance worsened (p < 0.05) and an altered pacing strategy was evident. Fatigue and total mood disturbance significantly increased across the cycle (p < 0.05), and trends were observed for reduced vigour and increased sleep disturbance (p < 0.1).ConclusionFour weeks of heavy training decreased RMR and body composition variables in elite rowers and induced substantial fatigue, likely related to an imbalance between energy intake and output. This study demonstrates that highly experienced athletes do not necessarily select the correct energy intake during periods of intensified training, and this can be assessed by reductions in RMR and body composition. The shortfall in energy availability likely affected recovery from training and altered 5 km time trial pacing strategy, resulting in reduced performance.

Winter Is Coming: Seasonal Variation in Resting Metabolic Rate of the European Badger (Meles meles).

Resting metabolic rate (RMR) is a measure of the minimum energy requirements of an animal at rest, and can give an indication of the costs of somatic maintenance. We measured RMR of free-ranging European badgers (Meles meles) to determine whether differences were related to sex, age and season. Badgers were captured in live-traps and placed individually within a metabolic chamber maintained at 20 ± 1°C. Resting metabolic rate was determined using an open-circuit respirometry system. Season was significantly correlated with RMR, but no effects of age or sex were detected. Summer RMR values were significantly higher than winter values (mass-adjusted mean ± standard error: 2366 ± 70 kJ⋅d−1; 1845 ± 109 kJ⋅d−1, respectively), with the percentage difference being 24.7%. While under the influence of anaesthesia, RMR was estimated to be 25.5% lower than the combined average value before administration, and after recovery from anaesthesia. Resting metabolic rate during the autumn and winter was not significantly different to allometric predictions of basal metabolic rate for mustelid species weighing 1 kg or greater, but badgers measured in the summer had values that were higher than predicted. Results suggest that a seasonal reduction in RMR coincides with apparent reductions in physical activity and body temperature as part of the overwintering strategy (‘winter lethargy’) in badgers. This study contributes to an expanding dataset on the ecophysiology of medium-sized carnivores, and emphasises the importance of considering season when making predictions of metabolic rate.

Abstract 25: Angiotensin AT 1A Receptors on Leptin Receptor-Expressing Cells are Required for the Blood Pressure and Metabolic Rate Effects of Leptin

Circulating leptin and the local brain renin-angiotensin system (RAS) both contribute to the control of food intake (FI), resting metabolic rate (RMR) and blood pressure (BP), and both have been postulated to contribute to obesity-hypertension. Here we examined the provocative hypothesis that the brain RAS is required for (or mediates) the RMR- and BP-stimulating effects of leptin. To create animals lacking the AT 1A receptor specifically in cells expressing the leptin receptor (“KO”), mice with a flox’ed version of the endogenous angiotensin AT 1A receptor gene (AT 1A flox ) were crossed with mice expressing cre-recombinase via the leptin receptor promoter (ObR-Cre). Body mass, body composition, blood chemistry, glucose tolerance, and FI behaviors were essentially unchanged through 34 weeks of age in mice maintained on standard chow (Teklad 7013). In contrast, anesthetized BP (MAP; control n=9, 91.6 ± 4.1, vs KO n=8, 78.0 ± 3.7 mmHg) and heart rate (351 ± 13, vs 308 ± 11 BPM) were reduced in KO mice (both P&lt;0.05). Further, interscapular brown adipose (BAT SNA, 112 ± 22, vs 22 ± 35 % above baseline at 3 hr) and renal (154 ± 19, vs 53 ± 23 % above baseline at 3 hr) sympathetic nerve activity responses to acute leptin injection (60 μg, i.v.) were completely abolished (both P&lt;0.05). When maintained on a 45% high fat diet (OpenSource D12451 ) to increase endogenous leptin production, KO mice exhibited accelerated body mass (control n=15, -0.1 ± 0.1, vs KO n=4, +1.7 ± 0.5 g/wk) and fat mass (+2.9 ± 0.5, vs +4.9 ± 1.1 g/5 wk) gains (both P&lt;0.05), likely due to normal FI behaviors but a 18% reduction in RMR (control n=16, 0.196 ± 0.011, vs KO n=7, 0.161 ± 0.004 kcal/hr at 30°C, P&lt;0.05). We conclude that expression of angiotensin AT 1A receptors on leptin-sensitive cells is required for the metabolic rate and cardiovascular effects of leptin. Ongoing studies are focused on identifying the brain regions and subsets of leptin receptor-expressing cells in which this RAS-leptin cross-talk occurs, and the directionality and molecular mediators of this interaction. We hypothesize that uncontrolled or pathological activity of the brain RAS may thus help explain the clinically variable effects of leptin, and contribute to the mechanism(s) of selective leptin resistance and obesity-hypertension.

Oral rapamycin does not mimic caloric restriction in mice

Rapamycin, an inhibitor of target of rapamycin (TOR), is the only known dietary additive that increases lifespan to the same extent as caloric restriction (CR). While mechanisms for lifespan extension remain unknown, both rapamycin and CR treatments influence signaling pathways that converge on TOR, an important regulator of growth and energy balance. We tested the hypothesis that similarities in lifespan extension of oral rapamycin and a 70% CR diet in mice would extend to physiological variables potentially important for the extension of life, including resting metabolic rate (RMR), heart rate (HR) and body temperature (Tb). C57BL/6J mice housed at 22°C were implanted with EKG telemeters, fed a control, rapamycin, or CR diet for 8 weeks, and then assessed for RMR via indirect calorimetry as well as HR and Tb via telemetry. CR mice, as compared to controls, showed dramatic reductions in minimal RMR (0.14±0.01 vs. 0.92±0.05 mL O2/min), HR (135±11 vs. 420±16 bpm) and Tb (25.7±0.2°C vs. 35.2 vs. 0.3°C). Rapamycin, however, had no significant impact on minimal RMR (0.85±0.07 mL O2/min), HR (405±17 bpm) or Tb (35.0±0.2°C) when compared to controls. These findings suggest that lifespan extension in rapamycin‐fed mice is not due to reductions in RMR, HR or Tb. Instead, it is likely that CR and rapamycin extend life though different mechanisms or that the treatments extend life via a mechanism that does not influence RMR, HR or Tb.

Energy Expenditure and Weight Regain in Patients Submitted to Roux-en-Y Gastric Bypass

Although Roux-en-Y gastric bypass (RYGBP) is a highly effective treatment for clinically severe obesity, not all patients achieve desirable weight loss and maintenance. There is some evidence that weight loss can induce a disproportionate reduction in resting metabolic rate (RMR). This reduction in RMR can be related to fat-free mass (FFM) loss, as FFM is the greatest responsible for variations in energy expenditure at rest. Abnormally low basal metabolic rate may predispose surgical patients to weight regain. Thirty-six individuals were divided into two groups: patients who have kept a healthy weight 2 years after surgery and patients who showed weight regain of at least 2 kg 2 years after the surgery. Selected patients have signed a consent form. Body mass index and excess weight loss were evaluated. RMR and body fat percentage were measured. FFM is a heterogeneous component that can be partitioned into muscle mass and no-muscle mass. The FFM was calculated as the result of subtracting total fat weight from total body weight in kilogram. We also wanted to know if the predictive formulas to assess RMR overestimate energy expenditure in these patients. Statistical tests were used to analyze the two groups. We found out that the RMR of the weight regain group was statistically inferior to the mean of the healthy weight group-the difference between the two groups was about 260 kcal/day. We also found out that the predictive formulas overestimate the RMR in the weight regain group. This study suggests that a lower RMR may contribute to weight regain in patients who undergo RYGBP. It is important to ensure ways to elevate energy expenditure in the patient, such as increasing the percentage of fat-free mass in the body and the practice of physical activities.

Physical Activity Level and Physical Functionality in Nonagenarians Compared to Individuals Aged 60-74 Years

Functional dependence and the risks of disability increase with age. The loss of independence is thought to be partially due to a decrease in physical activity. However, in populations, accurate measurement of physical activity is challenging and may not provide information on functional impairment. This study therefore assessed physical functionality and physical activity level in a group of nonagenarians (11 men/11 women; 93+/-1 years, 66.6+/-2.4 kg, body mass index [BMI]=24+/-1 kg/m2) and a group of participants aged 60-74 years (17 men/15 women; 70+/-1 years, 83.3+/-3.0 kg, BMI=29+/-1 kg/m2) from the Louisiana Healthy Aging Study. Physical activity level was calculated from total energy expenditure (TEE) and resting metabolic rate (RMR). Physical functionality was assessed using the Reduced Continuous Scale Physical Functional Performance Test (CS-PFP10). Nonagenarians had lower absolute (p<.001) and adjusted (p<.007) TEE compared to participants aged 60-74 years which was attributed to a reduction in both RMR and physical activity level. Nonagenarians also had reduced functional performance (p<.001) which was correlated with activity level (r=0.68, p<.001). When compared to individuals aged 60-74 years, 73% of the reduction in TEE in nonagenarians can be attributed to a reduction in physical activity level, the remaining being accounted for by a reduction in RMR. The reduced physical activity in nonagenarians is associated with less physical functionality. This study provides the first objective comparison of physical functionality and actual levels of physical activity in older individuals.

Ducklings Exhibit Substantial Energy‐Saving Mechanisms as a Response to Short‐Term Food Shortage

We investigated whether Pekin ducklings (Anas platyrhyncos domesticus) exhibited any energy-saving mechanisms that could lessen the detrimental effects of reduced food intake during early development. Further, we evaluated the role of body compositional changes behind such potential mechanisms and the consequences on thermoregulatory capacity. The ducklings exhibited substantial energy-saving mechanisms as a response to diet restriction. After 5 d of diet restriction, the resting metabolic rate (RMR) of 10- and 20-d-old ducklings was 16.4% and 32.1% lower, respectively, than predicted from body mass compared with ad lib. fed ducklings (controls). These reductions in RMR could have been adaptive responses in anticipation of a lasting food shortage, or they could have been consequences of the restricted diet and the lack of essential nutrients. We argue that the responses were adaptive. The low RMRs were not a consequence of depleted fuel stores because the diet-restricted ducklings exhibited substantial amounts of stored lipids at the end of the diet-restriction periods. Hypothermia accounted for approximately 50% of the reduction in RMR in the 10-d-old diet-restricted ducklings, but hypothermia did not occur in the 20-d-old diet-restricted ducklings. Diet restriction resulted in a reduced liver and intestine size and an unchanged size of the leg muscles and heart, while the length of the skull increased (compared with controls of a given body mass). However, changes in body composition were only minor predictors of the observed changes in RMR. Peak metabolic rate (PMR) was approximately 10% lower in the diet-restricted ducklings compared with the controls. We have interpreted the lower PMR as a consequence of the reductions in RMR rather than as a consequence of a decreased function of the thermoregulatory effector mechanisms.

Developmental plasticity of physiology and morphology in diet-restricted European shag nestlings (Phalacrocorax aristotelis)

Growing animals may exhibit developmental plasticity as an adaptation to variability in the environmental conditions during development. We examined physiological and morphological responses to short-term food shortage of 12-16-day-old European shag nestlings kept under laboratory conditions. After 4 days on a weight maintenance diet, the resting metabolic rate (RMR) of diet-restricted nestlings was 36.5% lower compared with control fed nestlings, after controlling for body mass. This response was accompanied by a reduction in body temperature (T(b)) and by reductions in the size of several visceral organs, muscles and lipid stores, while the overall structural growth was maintained almost in line with the age-specific growth rate of controls. Hence, the pattern of energy allocation reflected a very high priority to structural growth at the expense of visceral organs, lipid deposits and muscles. The reduced T(b) and size of the liver served as important physiological processes behind the observed reductions in RMR. We discuss the possible adaptive significance of this differential developmental plasticity during temporal food shortage. This is the first study of avian developmental plasticity to report substantial energy saving in combination with a high structural growth rate.