High Metabolic Rate Organs Research Articles

Fat-free mass and resting metabolic rate are determinants of energy intake: implications for a theory of appetite control.

Any explanation of appetite control should contain a description of physiological processes that could contribute a drive to eat alongside those that inhibit eating. However, such an undertaking was largely neglected until 15 years ago when a series of independent research programmes investigated the physiological roles of body composition and appetite. These outcomes demonstrated that fat-free mass (FFM), but not fat mass, was positively associated with objectively measured meal size and energy intake (EI). These findings have been accompanied by demonstrations that resting metabolic rate (RMR) is also positively associated with EI, with the influence of FFM largely mediated by RMR. These findings re-introduce the role of drive into models of appetite control and indicate how this can be integrated with processes of inhibition. The determinants of EI fit into an evolutionary perspective in which the energy demands of high metabolic rate organs and skeletal tissue constitute a need state underlying a tonic drive to eat. This approach should lead to the development of integrated models of appetite that include components of body composition (FFM) and energy expenditure (RMR) as tonic biological signals of appetite alongside other traditional tonic (adipose tissue derived) and episodic signals (gastrointestinal tract derived). This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part I)'.

COMPLEX EFFECT OF LOW-INTENSITY LASER RADIATION AND POTASSIUM CHANNEL PEPTIDE INHIBITOR ON MELANOMA CELL SURVIVAL

Melanoma is characterized by an aggressive development and a large number of metastases during diagnostics. Photodynamic therapy (PDT) is used to treat this type of cancer. However, the accumulation of photosensitizers is observed not only in malignant tumors, but also in high metabolic rate organs. Shortcomings of melanoma therapy can be eliminated using the complex effect of laser radiation and local administration of inhibitors of cellular processes.
 The goal. To study the complex effect of low-intensity laser radiation and potassium channel peptide inhibitor on melanoma cell survival.
 Materials and Methods. A875 melanoma cells were exposed to Kappa-theraphotoxin-Gr1b toxin and laser irradiation. The authors examined the level of apoptosis and necrosis in cells using fluorescence microscopy techniques. The xCELLigence system was used to assess the cytotoxic response of A875 melanoma cells.
 Results. The maximum number of apoptotic and necrotic cells was observed in the group of patients with A875 tumor cells exposed to a combination of Kappa-TRTX-Gr1b toxin and laser radiation (wavelength=1265 nm). This is due to the inhibition of potassium channels of intracellular cell membranes by Kappa-TRTX-Gr1b peptide, which are associated with the apoptosis.
 Conclusion. Selective potassium channel inhibition under pathological processes can be regarded as a significant supplement to the superficial malignant neoplasm complex therapy. The combination of toxin and irradiation will make it possible to potentiate their action and avoid the main PDT disadvantages. This approach unites the benefits of the local administration and precise exposure on the malignant tumor.

Associations between high-metabolic rate organ masses and fasting hunger: A study using whole-body magnetic resonance imaging in healthy males

BackgroundFat-free mass (FFM) has been shown to be positively associated with hunger and energy intake, an association mediated by resting metabolic rate (RMR). However, FFM comprises a heterogeneous group of tissues with distinct metabolic rates, and it remains unknown how specific high-metabolic rate organs contribute to the degree of perceived hunger. ObjectiveTo examine whether FFM and its anatomical components were associated with fasting hunger when assessed at the tissue-organ level. DesignBody composition (quantitative magnetic resonance and magnetic resonance imaging), RMR and whole-body glucose oxidation (indirect calorimetry), HOMA-index as a marker of insulin sensitivity, nitrogen balance and fasting hunger (visual analogue scales) were assessed in 21 healthy males (age = 25 ± 3y; BMI = 23.4 ± 2.1 kg/m2) after 3 days of controlled energy balance. ResultsFFM (rs = 0.39; p = 0.09), RMR (rs = 0.52; p = 0.02) and skeletal muscle mass (rs = 0.57; p = 0.04), but not fat mass (rs = −0.01; p = 0.99), were positively associated with fasting hunger. The association between the combined mass of high-metabolic rate organs (i.e., brain, liver, kidneys and heart; rs = 0.58; p = 0.006) and fasting hunger was stronger than with FFM as a uniform body component. The strongest individual association was between liver mass and fasting hunger (rs = 0.51; p = 0.02). No associations were observed between glucose parameters, markers of insulin sensitivity and fasting hunger. The encephalic measure, an index of brain-to-body energy allocation, was negatively associated with fasting hunger (rs = −0.51; p = 0.02). ConclusionsFasting hunger was more strongly associated with the combined mass of high-metabolic rate organs than with FFM as a uniform body component, highlighting the importance of integrating individual tissue-organ masses and their functional correlates into homeostatic models of human appetite. The association between liver mass and fasting hunger may reflect its role in ensuring the brain's basal energy needs are met.

A comparison of LKB1/AMPK/mTOR metabolic axis response to global ischaemia in brain, heart, liver and kidney in a rat model of cardiac arrest

BackgroundCellular energy failure in high metabolic rate organs is one of the underlying causes for many disorders such as neurodegenerative diseases, cardiomyopathies, liver and renal failures. In the past decade, numerous studies have discovered the cellular axis of LKB1/AMPK/mTOR as an essential modulator of cell homeostasis in response to energy stress. Through regulating adaptive mechanisms, this axis adjusts the energy availability to its demand by a systematized control on metabolism. Energy stress, however, could be sensed at different levels in various tissues, leading to applying different strategies in response to hypoxic insults.MethodsHere the immediate strategies of high metabolic rate organs to time-dependent short episodes of ischaemia were studied by using a rat model (n = 6/group) of cardiac arrest (CA) (15 and 30 s, 1, 2, 4 and 8 min CA). Using western blot analysis, we examined the responses of LKB1/AMPK/mTOR pathway in brain, heart, liver and kidney from 15 s up to 8 min of global ischaemia. The ratio of ADP/ATP was assessed in all ischemic and control groups, using ApoSENSOR bioluminescent assay kit.ResultsBrain, followed by kidney showed the early dephosphorylation response in AMPK (Thr172) and LKB1 (Ser431); in the absence of ATP decline (ADP/ATP elevation). Dephosphorylation of AMPK was followed by rephosphorylation and hyperphosphorylation, which was associated with a significant ATP decline. While heart’s activity of AMPK and LKB1 remained at the same level during short episodes of ischaemia, liver’s LKB1 was dephosphorylated after 2 min. AMPK response to ischaemia in liver was mainly based on an early alternative and a late constant hyperphosphorylation. No significant changes was observed in mTOR activity in all groups.ConclusionTogether our results suggest that early AMPK dephosphorylation followed by late hyperphosphorylation is the strategy of brain and kidney in response to ischaemia. While the liver seemed to get benefit of its AMPK system in early ischameia, possibly to stabilize ATP, the level of LKB1/AMPK activity in heart remained unchanged in short ischaemic episodes up to 8 min. Further researches must be conducted to elucidate the molecular mechanism underlying LKB1/AMPK response to oxygen supply.

Changes in skeletal muscle and organ size after a weight-loss intervention in overweight and obese type 2 diabetic patients

Background: The effect of a weight-loss intervention on the masses of lean tissues and organs in humans is not well known.Objective: We studied the effects of a diet and exercise weight-loss intervention on skeletal muscle (SM) mass and selected organs over 2 y using MRI in overweight adults with type 2 diabetes.Design: Participants were 53 women and 39 men [mean ± SD: age 58 ± 7 y; body mass index (BMI; in kg/m2) 32 ± 3] enrolled in the Look AHEAD (Action for Health in Diabetes) trial and randomly assigned to an intensive lifestyle intervention (ILI) or diabetes support and education (DSE) on whom 2 y of data were collected. MRI-derived measurements of SM, heart, liver, kidney, spleen, and pancreas were acquired.Results: Adjusted for baseline weight, height, age, sex, and ethnicity, the ILI group weighed (mean ± SE) 6.6 ± 0.7 kg less after 1 y and 5.2 ± 0.7 kg less after 2 y, whereas the DSE group did not change significantly (−0.4 ± 0.6 and −1.0 ± 0.7 kg after 1 and 2 y, respectively; P-interaction < 0.001). Total SM decreased in both groups during year 1 (−1.4 ± 0.2 kg; P < 0.001) with appendicular SM regained during year 2. Liver and spleen masses decreased in the ILI group (−0.12 ± 0.02 and −0.006 ± 0.003 kg, respectively) but were unchanged in the DSE group (0.00 ± 0.02 and 0.004 ± 0.003 kg, respectively). Kidney mass decreased by 0.013 ± 0.003 kg (P < 0.001) over 2 y in both groups.Conclusions: Decreases in liver (in Caucasians but not African Americans) and spleen were detected after a 6.2-kg weight reduction compared with a control group. SM and kidney mass decreased in both groups. Appendicular SM was regained during the second year whereas trunk SM was not. No evidence of a disproportionate loss of high–metabolic rate organs (heart, liver, kidney, spleen) compared with SM was found.

Age-Dependent Changes in Resting Energy Expenditure (REE): Insights from Detailed Body Composition Analysis in Normal and Overweight Healthy Caucasians.

Age-related changes in organ and tissue masses may add to changes in the relationship between resting energy expenditure (REE) and fat free mass (FFM) in normal and overweight healthy Caucasians. Secondary analysis using cross-sectional data of 714 healthy normal and overweight Caucasian subjects (age 18–83 years) with comprehensive information on FFM, organ and tissue masses (as assessed by magnetic resonance imaging (MRI)), body density (as assessed by Air Displacement Plethysmography (ADP)) and hydration (as assessed by deuterium dilution (D2O)) and REE (as assessed by indirect calorimetry). High metabolic rate organs (HMR) summarized brain, heart, liver and kidney masses. Ratios of HMR organs and muscle mass (MM) in relation to FFM were considered. REE was calculated (REEc) using organ and tissue masses times their specific metabolic rates. REE, FFM, specific metabolic rates, the REE-FFM relationship, HOMA, CRP, and thyroid hormone levels change with age. The age-related decrease in FFM explained 59.7% of decreases in REE. Mean residuals of the REE-FFM association were positive in young adults but became negative in older subjects. When compared to young adults, proportions of MM to FFM decreased with age, whereas contributions of liver and heart did not differ between age groups. HOMA, TSH and inflammation (plasma CRP-levels) explained 4.2%, 2.0% and 1.4% of the variance in the REE-FFM residuals, but age and plasma T3-levels had no effects. HMR to FFM and MM to FFM ratios together added 11.8% on to the variance of REE-FFM residuals. Differences between REE and REEc increased with age, suggesting age-related changes in specific metabolic rates of organs and tissues. This bias was partly explained by plasmaT3-levels. Age-related changes in REE are explained by (i) decreases in fat free mass; (ii) a decrease in the contributions of organ and muscle masses to FFM; and (iii) decreases in specific organ and tissue metabolic rates. Age-dependent changes in the REE-FFMassociation are explained by composition of FFM, inflammation and thyroid hormones.

Relationship between submaximal oxygen uptake, detailed body composition, and resting energy expenditure in overweight subjects

We investigated the impact of detailed body composition on aerobic fitness to determine whether regional components of fat mass have independent effects on VO2submax , and whether VO2submax and detailed body composition independently explain variation in REE. 71 healthy adults (80% female, 20% male, BMI 28.2-43.8 kg/m(2) ) were investigated. Body composition was measured by the four-compartment model together with whole body magnetic resonance imaging (MRI) to assess high and low metabolic rate organs and regional fat depots. VO2submax was estimated at 75% of predicted maximum heart rate. There was a strong association between VO2submax and FFM and all organ masses except for heart. Skeletal muscle mass accounted for 34.8% of the variance in VO2submax . In addition, subcutaneous adipose tissue (SAT) of extremities explained additional 14.4%. FFM and FM explained 71.3% of the variance in REE. Including the components of FFM and FM, the explained variance in REE increased by about 5.8%; skeletal muscle mass explained 70.0% of the variance in REE and kidney and liver masses explained additional 7.1%. VO2submax correlated with REE. Taking into account body composition, VO2submax did not add to the variance in REE. FFM is a determinant of both VO2submax and REE. Modeling either REE or VO2submax from individual components of FFM, about 77.1% of variance in REE (by muscle, liver and kidneys mass) and 34.8% of variance in VO2submax (by skeletal muscle mass) could be explained. FM explained additional variance in REE, whereas SAT of extremities added to the variance in VO2submax only.

High ratio of resting energy expenditure to body mass in childhood and adolescence: A mechanistic model

Children have lower resting energy expenditure (REE) but higher ratio of resting energy expenditure to body mass (REE/BM) than do adults. This well-known observation has never been quantitatively explained. The aim of the present study is to understand the high REE/BM in childhood and adolescence. A mechanistic REE/BM model is proposed. Literature data on REE, BM and the masses of four high metabolic rate organs (i.e., liver, brain, heart and kidneys) of 1-18 y boys and girls were used to evaluate the proposed REE/BM model. Specifically, we tested the hypothesis that the magnitude and variation of the REE/BM can be predicted by a combination of four variables, including relative cellularity, growth energy expenditure for constructing new cells, fraction of body mass as individual organs/tissues, and their specific resting energy expenditure. The REE/BM provided by the literature is 54 kcal/kg per day at 1 year, decreasing to 26.0 kcal/kg per day at 18 years. Model-predicted REE/BM can account for 97.0% and 100.7% of the literature-reported REE/BM in males and females, respectively. The average differences between literature-reported and model-predicted REE/BM are 1.1 kcal/kg per day in boys and -0.3 kcal/kg per day in girls. The high REE/BM ratio in childhood results from two model variables: the high fraction of body mass as liver, brain, heart, and kidneys, and their high specific resting metabolic rates. The proposed REE/BM model promotes understanding of the REE, and allows a rational establishment of energy requirements for children and adolescents.

European ancestry and resting metabolic rate in older African Americans

Resting metabolic rate (RMR) contributes 60-80% of total energy expenditure and is consistently lower in populations of African descent compared with populations of European populations. Determination of European ancestry (EA) through single nucleotide polymorphism (SNP) analysis would provide an initial step for identifying genetic associations that contribute to low RMR. We sought to evaluate the association between RMR and EA in African Americans. RMR was measured by indirect calorimetry in 141 African American men and women (aged 74.7±3.0 years) enrolled in a substudy of the Health, Aging and Body Composition Study. Ancestry informative markers were used to estimate individual percent EA. Multivariate regression was used to assess the association between RMR and EA after adjustments for soft tissue fat-free mass (STFFM), fat mass, age, study site, physical activity level and sex. Mean EA was 23.8±16% (range: 0.1-70.7%) and there were no differences by sex. Following adjustments, each percent EA was associated with a 1.6 kcal/day (95% Confidence interval: 0.42, 2.7 kcal/day) higher RMR (P=0.008). This equates to a 160 kcal/day lower RMR in a population of completely African ancestry, with one of completely European ancestry. Additional adjustment for trunk STFFM that partially accounts for high-metabolic rate organs did not affect this association. EA in African Americans is strongly associated with higher RMR. The data suggest that population differences in RMR may be due to genetic variants.

Brain and high metabolic rate organ mass: contributions to resting energy expenditure beyond fat-free mass

The degree to which interindividual variation in the mass of select high metabolic rate organs (HMROs) mediates variability in resting energy expenditure (REE) is unknown. The objective was to investigate how much REE variability is explained by differences in HMRO mass in adults and whether age, sex, and race independently predict REE after adjustment for HMRO. A cross-sectional evaluation of 55 women [30 African Americans aged 48.7 +/- 22.2 y (mean +/- SD) and 25 whites aged 46.4 +/- 17.7 y] and 32 men (8 African Americans aged 34.3 +/- 18.2 y and 24 whites aged 51.3 +/- 20.6 y) was conducted. Liver, kidney, spleen, heart, and brain masses were measured by magnetic resonance imaging, and fat and fat-free mass (FFM) were measured by dual-energy X-ray absorptiometry. REE was measured by indirect calorimetry. REE estimated from age (P = 0.001), race (P = 0.006), sex (P = 0.31), fat (P = 0.001), and FFM (P < 0.001) accounted for 70% (adjusted (2)) of the variability in REE. The addition of trunk HMRO (P = 0.001) and brain (P = 0.006) to the model increased the explained variance to 75% and rendered the contributions of age, sex, and race statistically nonsignificant, whereas fat and FFM continued to make significant contributions (both P < 0.05). The addition of brain to the model rendered the intercept (69 kcal . kg(-1) . d(-1)) consistent with zero, which indicated zero REE for zero body mass. Relatively small interindividual variation in HMRO mass significantly affects REE and reduces the role of age, race, and sex in explaining REE. Decreases in REE with increasing age may be partly related to age-associated changes in the relative size of FFM components.

The Impact of Visceral Mass on Survival in Chronic Hemodialysis Patients

In chronic hemodialysis, patient survival is positively correlated with body weight and body mass index (BMI). This relationship extends even to obese patients with a BMI >30 kg/m2. We have put forward the hypothesis that this survival benefit may be due to a lower average synthesis rate of uremic toxins (expressed as amount per time per unit of body weight) in larger patients, because the relative contribution of the high metabolic rate organs (HMRO) to body weight in these patients is lower and HMRO are most likely to be the prime source of uremic toxins. In addition, the average uremic toxin concentration in larger patients may be lower because of the larger distribution volume. Based on these assumptions, a better survival in patients with a lower HMRO to body weight fraction (HMRO%BW) can be predicted. To test this hypothesis we estimated gender- and race-specific HMRO mass by means of recently published regression models in 2,004 incident hemodialysis patients. Cox proportional hazards models were used to assess the association between age, serum albumin concentration, eKt/V, and HMRO% BW and mortality. High HMRO%BW was significantly associated with increased mortality (hazard ratio 1.323 [95% CI: 1.186 to 1.477]). Mean survival time was longest in the low HMRO%BW tertile (1,031 days [95%CI: 974 to 1,087]), 935 days [95%CI: 886 to 984] in the middle, and 876 days [95%CI: 825 to 926] in the high HMRO%BW tertile (p<0.0001; log rank test). These results support the hypothesis predicting that a low HMRO mass per unit of weight confers a beneficial effect on survival.

Resting energy expenditure-fat-free mass relationship: new insights provided by body composition modeling.

The relationship between resting energy expenditure (REE) and metabolically active fat-free mass (FFM) is a cornerstone in the study of physiological aspects of body weight regulation and human energy requirements. Important questions, however, remain unanswered regarding the observed linear REE-FFM association in adult humans. This led us to develop a series of REE-body composition models that provide insights into the widely used simple linear REE-FFM prediction model derived experimentally in adult humans. The new models suggest that the REE-FFM relationship in mammals as a whole is curvilinear, that a segment of this function within a FFM range characteristic of adult humans can be fit with a linear equation almost identical to that observed from a composite review of earlier human studies, and that mammals as a whole exhibit a decrease in the proportion of FFM as high metabolic rate organs with greater FFM. The present study thus provides a new approach for examining REE-FFM relationships, advances in a quantitative manner previously observed albeit incompletely formulated REE-body composition associations, and identifies areas in need of additional research.