Higher Basal Metabolic Rate Research Articles

A bidirectional Mendelian randomization study supports the causal effects of a high basal metabolic rate on colorectal cancer risk.

PurposeWe conducted a bidirectional two-sample Mendelian randomization (MR) study to determine whether genetically predicted basal metabolic rate (BMR) was a causal risk factor for colorectal cancer (CRC) or whether a genetically predicted CRC risk can influence the BMR level (i.e., reverse causation).MethodsWe employed 1,040 genetic variants as proxies for BMR to obtain effect estimates on CRC risk. Another 58 CRC-associated variants were used to estimate effects on BMR levels. Stratified analysis by tumor site was used to examine the causal associations between BMR and colon/rectal cancer risk.ResultsThe inverse variance weighted (IVW) method indicated a significant causal effect of genetically determined BMR on CRC risk (ORSD = 1.27, 95% CI = 1.07–1.51). No significant reverse causal association was identified between genetically increased CRC risk and BMR levels [IVW (β = 0, 95% CI = -0.01 to 0)]. The results of MR-Egger and the weighted median method were consistent with the IVW method. Stratified analysis by CRC sites identified significant causal associations between BMR and colon cancer [IVW (ORSD = 1.45, 95% CI = 1.16-1-80)], and null evidence of a causal association between BMR and rectal cancer risk was found (p > 0.05).ConclusionOur findings add to the current literature by validating a positive relationship between high BMR levels and CRC risk instead of reverse causality. The genetically predicted BMR level was causally associated with colon cancer risk but not rectal cancer risk.

Prevalence of obesity and effect of sport activity on university students in Algeria

Overweight and obesity have become major public health problems affecting most countries worldwide. This article describes the prevalence of overweight and obesity among adult students from Relizane University (western Algeria) and assesses their sports activity, basal metabolism and the relationship between sports activity, basal metabolism and gender. A descriptive survey questionnaire was carried out on 363 students (125 (34.43%) males and 238 (65.56%) females) aged 21.55 ± 2.6 years old. It included open-ended and closed questions and covered the following topics: demographic information (age, gender), anthropometric parameters (body weight, height, waist measurement and hip measurement), sports activity and sleep duration. Moreover, body mass index (BMI) was calculated and relation with sports activity, basal metabolism and gender were assessed. Results showed that 80 students (22.04%) were overweight and 23 students (6.34%) were obese. The number of students with normal BMI (18-24) was 235 (64.74%) and those with BMI <18 were 25 (6.89%). Females had a significantly high waist circumference than males (83.08 ± 11.29 cm vs. 78.64 ± 9.43 cm). There was a strong positive correlation between BMI and waist circumference for females (r = 0.656; p < 0.001) and males (r = 0.697; p < 0.001). Among 363 students enrolled in the study, 171 students were involved in a sporting activity (47.11%) and the duration of sports activity per session for males (1.33 ± 0.4 h; p < 0.001) was significantly higher than for females (1.24 ± 0.54 h). For the four BMI categories, women had significantly lower basal metabolic rates than men. In addition, obese and overweight students have higher basal metabolic rates than students who are normal weight, while underweight students have lower basal metabolic rates (p 0.001). This survey highlighted the prevalence of obesity among students; it can be managed using planning informational and promotional programs for students to encourage their participation in various physical activities.

Mice selected for a high basal metabolic rate evolved larger guts but not more efficient mitochondria.

Intra-specific variation in both the basal metabolic rate (BMR) and mitochondrial efficiency (the amount of ATP produced per unit of oxygen consumed) has profound evolutionary and ecological consequences. However, the functional mechanisms responsible for this variation are not fully understood. Mitochondrial efficiency is negatively correlated with BMR at the interspecific level but it is positively correlated with performance capacity at the intra-specific level. This discrepancy is surprising, as theories explaining the evolution of endothermy assume a positive correlation between BMR and performance capacity. Here, we quantified mitochondrial oxidative phosphorylation activity and efficiency in two lines of laboratory mice divergently selected for either high (H-BMR) or low (L-BMR) levels of BMR. H-BMR mice had larger livers and kidneys (organs that are important predictors of BMR). H-BMR mice also showed higher oxidative phosphorylation activity in liver mitochondria but this difference can be hypothesized to be a direct effect of selection only if the heritability of this trait is low. However, mitochondrial efficiency in all studied organs did not differ between the two lines. We conclude that the rapid evolution of BMR can reflect changes in organ size rather than mitochondrial properties, and does not need to be accompanied obligatorily by changes in mitochondrial efficiency.

Brain size, gut size and cognitive abilities: the energy trade-offs tested in artificial selection experiment.

The enlarged brains of homeotherms bring behavioural advantages, but also incur high energy expenditures. The ‘expensive brain’ (EB) hypothesis posits that the energetic costs of the enlarged brain and the resulting increased cognitive abilities (CA) were met by either increased energy turnover or reduced allocation to other expensive organs, such as the gut. We tested the EB hypothesis by analysing correlated responses to selection in an experimental evolution model system, which comprises line types of laboratory mice selected for high or low basal metabolic rate (BMR), maximum (VO2max) metabolic rates and random-bred (unselected) lines. The traits are implicated in the evolution of homeothermy, having been pre-requisites for the encephalization and exceptional CA of mammals, including humans. High-BMR mice had bigger guts, but not brains, than mice of other line types. Yet, they were superior in the cognitive tasks carried out in both reward and avoidance learning contexts and had higher neuronal plasticity (indexed as the long-term potentiation) than their counterparts. Our data indicate that the evolutionary increase of CA in mammals was initially associated with increased BMR and brain plasticity. It was also fuelled by an enlarged gut, which was not traded off for brain size.

Investigating Body Mass Index and Body Composition in Patients with Schizophrenia: A Case-Control Study.

Background Antipsychotics exert metabolic side effects, and prolonged treatment with antipsychotics causes changes in body weight and muscle composition. Nevertheless, reports on the changes in body composition of patients with schizophrenia have been limited. This study is aimed at comparing the body mass index and body composition of patients with schizophrenia with healthy individuals in Indonesia. Methods A total of 195 patients with schizophrenia (148 males and 47 females) and 195 healthy individuals matched by gender were recruited. Using the Bioelectrical Impedance Analysis method, the participants' body compositions were measured. Results Compared to healthy individuals, the patient group exhibited a higher rate of underweight as well as a lower rate of overweight and obesity. Multiple regression analysis confirmed the associations between the body mass index and all measured body compositions. Furthermore, the diagnosis of schizophrenia is significantly associated with lower muscle mass, lower bone mass, higher basal metabolic rate, older metabolic age, and higher total body water. Conclusions The results showed that patients with schizophrenia are at a greater risk of a lower quality of certain components of body composition. Priority should be given to research that addresses increasing the patient's level of physical activity.

Differences in advanced glycation endproducts (AGEs) in plasma from birds and mammals of different body sizes and ages

Birds and mammals provide a physiological paradox: similar-sized mammals live shorter lives than birds; yet, birds have higher blood glucose concentrations than mammals, and higher basal metabolic rates. We have previously shown that oxidative stress patterns between mammals and birds differ, so that birds, generally, have lower blood antioxidant capacity, and lower lipid peroxidation concentration. There is a close association between oxidative stress and the production of carbohydrate-based damaged biomolecules, Advanced Glycation End-products (AGEs). In mammals, AGEs can bind to their receptor (RAGE), which can lead to increases in reactive oxygen species (ROS) production, and can decrease antioxidant capacity. Here, we used plasma from birds and mammals to address whether blood plasma AGE-BSA concentration is associated with body mass and age in these two groups. We found a statistically significantly higher average concentrations of AGE-BSA in birds compared with mammals, and we found a significantly positive correlation between AGE-BSA and age in mammals, though, this correlation disappeared after phylogenetic correction. We propose that the higher AGE concentration in birds is mainly attributable to greater AGE-production due to elevated basal glucose concentrations and decreased AGE-clearance given differences in glomerular filtration rates in birds compared with mammals. Additionally, due to the potential lack of an AGE receptor in birds, AGE accumulation may not be closely linked to oxidative stress and therefore pose a lesser physiological challenge in birds compared to mammals.

Establishing and Maintaining an Etruscan Shrew Colony.

The Etruscan shrew (Suncus etruscus) is one of the smallest mammals on earth and is used in many fields of research, including physiology, behavioral science and neuroscience. However, establishing and maintaining a breeding colony of this species in the laboratory can be challenging, as it requires specific husbandry conditions that greatly differ from those of more common laboratory species such as mice or rats. Over the past 15 y, we have successfully established a long-term thriving colony of 150 to 200 animals originating from 36 founders. The colony shows longer life expectancy and larger litter sizes than wild conspecifics. Breeding occurs year-round, independent of seasons, and a breeding pair can regularly produce 2 to 6 offspring with an average life expectancy of more than 3 y. The shrews are housed in glass or plastic enclosures on a specific soil-sand-mixture bedding and are provided with hideouts and nesting material consisting of moss, wood, or bark. Due to their high basal metabolic rate, the shrews require food intake greater than their body weight per day, can hunt arthropods as large as themselves, and cannot survive more than a few hours without food. Live feed such as crickets or mealworms is crucial and must be provided daily or, at the very least, every 2 d. Although our husbandry practices have constantly been adapted and refined, shrew husbandry remains challenging, and great care is necessary to meet the specific needs of this species. Here, we describe the establishment of a long-term stable colony of Etruscan shrews in a research animal facility and the specific husbandry requirements for animal wellbeing.

The Prevalence of Malnutrition and its Impact on Children with Congenital Heart Disease in Post Cardiac Surgery

Background: Children with congenital heart disease (CHD) require adequate nutrition for growth and development. Children with CHD are often malnourished and with dyspnea, leading to failure to thrive. Children with CHD have a high basal metabolic rate leading to high caloric requirement. Objective: To evaluate the prevalence ofmalnutrition and its impact on children with congenital heart disease in post cardiac surgery. Method: This cross-sectional study was carried out at Bangladesh Shishu Hospital and Institute, Bangladesh. Data were collected from January 2019 to January 2020. A total of 40 pediatric patients with CHD admitted for cardiac surgery were included in the study. Sample were collected through purposive sampling as per inclusion criteria. Results: During the study, most of the children belonged to 1 year to 5 years of age group and 60% were male. The nutritional status of the patients before surgery was defined as normal 55%, malnutrition 45%. In malnutrition group heart defect cases was higher than that of normal group. Mean z score for A/W(SEM) was -1.05 in normal group and -3.06 in malnutrition group. Malnourished patients clearly showed a tendency (P=0.005) to have a longer length of intubation, i.e., mean 35.67 hours when compared with those with a normal nutritional status who have mean intubation time of 27.51 hours. The other morbidity factor measured was the length of ICU stay, which also showed a significant result. Conclusion: In Bangladesh, malnutrition is frequent among children with congenital cardiac defects which increases risk of morbidity related with prolonged mechanical ventilation and ICU stays. To minimize potentially harmful effects, the health care system should be able to screen and identify these individuals early on.

Larger guts and faster growth in mice selected for high basal metabolic rate.

Postnatal growth in birds and mammals is the time of highest vulnerability and relatively high energy demands and therefore shapes the organisms' future outcomes. Several different factors might impose limitations on growth in juveniles, one of them being the efficiency of the digestive process and size of the gastrointestinal tract. We tested the gut size-growth rate relationship using a unique experimental model-mice from a selection experiment designed to produce two lines with divergent levels of basal metabolic rate (BMR): the high BMR (H-BMR) and low BMR (L-BMR) line types. These lines differ with respect to not only BMR, but also correlated traits-internal organ size and food intake. Applying a cross-fostering design and a thermoregulatory burden imposed by shaving the mothers, we demonstrated that the mass of intestine strongly affected the growth rate, with the H-BMR pups having larger intestines and growing faster, and with reduced growth rate of pups of both lines nursed by shaved L-BMR mothers. Our study also provides a functional link between high growth rate of neonates and high BMR of adults, partly reflecting metabolic costs of maintenance of their guts.

DIABETES OR OBESITY; MAJOR EFFECTOR OF ALTERED LEVELS OF GHRELIN AND LEPTIN

Background: Ghrelin and leptin are the key hormones involved in the energy homeostasis and plays a relevant role in regulating hunger and satiety stimuli afferent to the brain. Abnormalities in the levels of ghrelin and leptin are often associated with the obesity and type 2 diabetes complications. However, there are no studies clarifying whether ghrelin and leptin levels have stronger association with obesity or Type 2 diabetes (T2DM). Aims:To evaluate and compare the independent effect of major dening factors of obesity and diabetes on ghrelin and leptin concentrations. Materials And Methods: Anthropometric measures such as height, weight, waist (WC) and hip circumference (HC), Body mass index (BMI), Basal metabolic rate (BMR), fat percentage, lean body mass, were taken. Assessed daily physical activity and energy intake. Biochemical parameters such as fasting glucose, postprandial glucose, HBA1c, ghrelin, leptin and insulin levels were measured. Statistical Analysis: One-way analysis of variance (ANOVA), Chi-square (χ2) test Pearson's correlation coefcients, Multiple stepwise linear regression model analysis were performed. Result: The diabetic subjects irrespective of obesity showed signicantly higher waist to hip ratio, HOMAIR levels of fasting blood glucose, postprandial glucose and signicantly lower levels of Ghrelin than non-diabetics. Similarly, obese subjects irrespective of diabetes have signicantly higher BMR and higher levels of Leptin than non-diabetics. Asignicantly higher BMI, fat mass percentage and lower lean body mass percentage were observed in obese subjects irrespective of diabetes than non-obese subjects. Among non-obese, diabetics have higher BMI, Fat mass percentage and lower lean body mass percentage. The levels of insulin were signicantly higher in diabetic obese subjects. HOMAIR (P≤0.0001) and Postprandial glucose (P≤0.05) showed negative independent effect and QUICKI (P≤0.0001) showed positive independent effect on the levels of ghrelin. BMI (P≤0.05) showed a positive effect and lean body mass percentage (P≤0.0001) showed an inverse effect on levels of leptin. Conclusion: It is evident from the study that low levels of ghrelin are predominantly associated with diabetes parameters when compared to parameters of obesity and on the contrary increased leptin levels have much stronger association with measures of obesity than diabetes. Evidence of altered leptin and ghrelin levels in these disorders infers vice versa, their respective roles in obesity and lean diabetes.

The high-energy aerial insectivore lifestyle of swallows does not produce clear thermogenic side effects

Abstract Ecological traits related to pace of life, such as foraging strategies and activity levels, influence daily energy expenditure (DEE) and can affect fitness. A fast pace of life tends to be supported by high-energy aerobic activity and is positively correlated with high DEE and basal and maximal metabolic rates in some endotherms. Given that maximal capacities for exercise and thermogenesis are both functions of aerobic muscle output and are often positively correlated with each other, high-energy aerobic lifestyles might be associated with high aerobic capacities, which would be expected to produce high thermogenic capacities as a side effect. We tested whether the high-energy aerial insectivore lifestyle in swallows is correlated with elevated basal and maximal thermogenic metabolic rates. We measured basal (BMR) and summit (Msum = maximum cold-induced metabolic rate) metabolic rates in 6 species of swallows (Hirundinidae) and combined these data with literature data for additional swallows (n = 10 for BMR; n = 8 for Msum) and non-aerial insectivore birds (n = 215 for BMR; n = 64 for Msum) to address the hypothesis that swallows have higher BMR and Msum than non-aerial insectivores. BMR in swallows was significantly higher than for non-aerial insectivore birds for phylogenetically adjusted analyses after correcting for body mass and region of origin (tropical vs. temperate). In contrast, Msum did not differ significantly between swallows and non-aerial insectivores. Thermogenic scope (Msum – BMR), however, was lower in tropical non-aerial insectivore birds compared with tropical swallows and temperate birds. This suggests that the aerial insectivore lifestyle elevates maintenance costs, but maximum thermogenic capacities are not clearly upregulated, despite tropical swallows having higher thermogenic scope than tropical non-aerial insectivores. These data suggest that the high-energy aerial insectivore lifestyle does not produce strong thermogenic side effects in swallows.

Body composition and health behaviors among older women attending regular fitness classes: a pilot study

Background: The average lifespan is increasing worldwide, although the healthspan and quality of life is not. Many older adults either have a chronic disease, excessive body mass, or do not follow the healthy lifestyle recommendations as for nutrition and physical activity. Aim of the study: This study aimed to assess the relationship between body composition among senior women and health behaviors in the five domains of nutrition, body care, rest, safety and physical activity. Material and methods: The study group consisted of 36 women attending fitness classes. The Positive Health Behavior Questionnaire was used as the qualitative measurement and participant height, weight and body composition were measured. Body Mass Index (BMI), Waist-to-Hip Ratio (WHR ), Basal Metabolic Rate (BMR) were calculated. Results: Significant correlations (p≤0.05) were found between attending organized physical activities and higher muscle mass and higher BMR. Moreover, (a) sleeping at least six to seven hours at night correlated with a lower BMI and lower body fat mass; (b) spending at least 20–30 minutes a day resting correlated with lower visceral fat; (c) devoting at least 30 minutes daily to moderate or heavy physical exertion correlated with lower body fat mass, percent of body fat and visceral adiposity. Conclusions: The study shows strong relationships between physical activity, dietary patterns, rest, length of sleep, BMI, adiposity and muscle mass of physically active senior women. The results suggest it is necessary to actively promote and support older women in implementing healthy behaviors consistently in their life.

Polymorphism of winter phenotype in Siberian hamster: consecutive litters do not differ in photoresponsiveness but prolonged acclimation to long photoperiod inhibits winter molt

BackgroundThe theory of delayed life history effects assumes that phenotype of adult individual results from environmental conditions experienced at birth and as juvenile. In seasonal environments, being born late in the reproductive season affects timing of puberty, body condition, longevity, and fitness. We hypothesized that late-born individuals are more prone to respond to short photoperiod (SP) than early born ones. We used Siberian hamsters Phodopus sungorus, a model species characterized by high polymorphism of winter phenotype. We experimentally distinguished the effect of litter order (first or third) from the effect of exposure to long photoperiod (LP) before winter (3 months or 5 months) by manipulating the duration of LP acclimation in both litters. We predicted that, irrespective of the litter order, individuals exposed to long photoperiod for a short time have less time to gather energy resources and consequently are more prone to developing energy-conserving phenotypes. To assess effect of litter order, duration of acclimation to long days, and phenotype on basal cost of living we measured basal metabolic rate (BMR) of hamsters.ResultsIndividuals born in third litters had faster growth rates and were bigger than individuals from first litters, but these differences vanished before transfer to SP. Litter order or duration of LP acclimation had no effects on torpor use or seasonal body mass changes, but prolonged acclimation to LP inhibited winter molting both in first and third litters. Moreover, individuals that did not molt had significantly higher BMR in SP than those which molted to white fur. Although one phenotype usually predominated within a litter, littermates were often heterogeneous. We also found that over 10% of individuals presented late response to short photoperiod.ConclusionsOur data indicate that duration of postnatal exposure to LP may define propensity to photoresponsiveness, regardless of the litter in which animal was born. Existence of littermates presenting different phenotypes suggests a prudent reproductive strategy of investing into offspring of varied phenotypes, that might be favored depending on environmental conditions. This strategy could have evolved in response to living in stochastic environment.

A high basal metabolic rate is an independent predictor of stone recurrence in obese patients.

PurposeBasal metabolic rate (BMR) is an indicator of overall body metabolism and may portend unique aberrations in urine physico-chemistry and stone recurrence. The present study examined the effect of predicted BMR on 24 hours urinary metabolic profiles and stone recurrence in obese stone patients.Materials and MethodsData from 308 obese patients (body mass index [BMI] ≥30 kg/m2) diagnosed with urinary stone disease between 2003 and 2015 were analyzed retrospectively. BMR was calculated using the Harris–Benedict equation, and patients were classified into two predicted BMR categories (<1,145 kcal/day, ≥1,145 kcal/day). Urinary metabolic parameters and risk of stone recurrence were compared between the two groups.ResultsThe high BMR group was more likely to be younger and female, and to have a high BMI and lower incidence of diabetes than the low BMR group (each p<0.05). There was a positive correlation between BMR and 24 hours urinary sodium, uric acid, and phosphate excretion. The amounts of stone-forming constituents such as calcium and uric acid were significantly higher in the high BMR group. Kaplan–Meier estimates showed that the high BMR group had a significantly shorter stone recurrence-free period than the low BMR group (log-rank test, p<0.001). Multivariate Cox regression analyses revealed that predicted BMR was an independent factor of stone recurrence (hazard ratio, 2.759; 95% confidence interval, 1.413–5.386; p=0.003).ConclusionsBMR may be an easily measured parameter that can be used to identify risk of stone recurrence in obese stone patients.

Multiparametric evaluation of coronary flow predicts long-term outcome in heart transplantation: from coronary flow velocity reserve to its newly introduced companion

Abstract Background Coronary microvascular dysfunction (CMD) leads to a worse prognosis in heart transplantation (HT) patients. Coronary flow velocity reserve (CFVR) estimates the physiologic impact of allograft disease on the coronary circulation. Purpose Our aim was to determine the prognostic role of CFVR and its companion (CFVRC) on long-term survival of HT patients with a follow-up of 28 years. Methods 134 HT patients, surviving at least 5 years after HT, with normal systolic ventricular function and no evidence of angiographic allograft vasculopathy or symptoms/signs of rejection were included. The enrolled population underwent echocardiographic evaluation of microvascular function by the assessment of both the ratio of hyperemic to rest diastolic peak velocity (DPVh and DPVr). These measurements yield CFVR and its associated companion, defined as CFVRC = √{(DPVr)2 + (DPVh)2}, as well as basal and hyperemic coronary microvascular resistance (BMR and HMR). A CFVR≤2.5 was considered abnormal; the median value of DPVh (75 cm/s) and CFVRC (80 cm/s) were utilized to dichotomize the population. Results Based on CFVR and DPVh, HT patients can be assigned to four groups: group 1 (n=32), discordant with preserved CFVR (3.1±0.4); group 2 (n=60), concordant with preserved CFVR (3.4±0.5); group 3 (n=31), concordant with impaired CFVR (1.8±0.3) and group 4 (n=11), discordant with impaired CFVR (2.0±0.2). Survival for each patient group is presented in the Figure (panel A). Specifically, survival was similar in group 1 when compared to group 3 (p=0.8), but significantly lower when compared to group 2 (p=0.03). Therefore, a normal CFVR (&amp;gt;2.5) may not be able to predict the unfavourable long-term outcome. CFVR in fact is an incomplete dimensionless ratio; if the paired velocities are low with high BMR and HMR (group 1), the use of CFVR alone may miss some events, that are yet captured by CFVRC. Differences between survivors and no survivors are presented in the Table. At multivariable survival analysis, CMD, DPVh&amp;lt;75 cm/s, CFVRC&amp;lt;80 cm/s were independent predictors of mortality in HT patients. Consequently, we evaluated the added role of the CMD, DPVh&amp;lt;75 cm/s and CFVRC&amp;lt;80 cm/s to prognostic models including the clinical (Figure, panel B) predictors of mortality. The inclusion of CFVRC&amp;lt;80 cm/s to model with clinical predictors of mortality permitted better prediction of survival in HT patients, compared to only adding CMD or DPVh&amp;lt;75 cm/s. Conclusions This study is the first to demonstrate that the CFVR alone, even representing a determinant of survival in long-term HT patients, is not sufficient to completely predict long-term survival in HT patients. In comparison to CMD and DPVh, the CFVRC provides a significant improvement in survival prediction in long-term HT patients. Thus, the proposed multiparametric approach offers a more comprehensive evaluation of prognosis in HT patients, just by applying available data without the need to perform additional measurements. Funding Acknowledgement Type of funding source: None

Low basal metabolic rate as a risk factor for development of insulin resistance and type 2 diabetes

IntroductionIdentification of physiological factors influencing susceptibility to insulin resistance and type 2 diabetes (T2D) remains an important challenge for biology and medicine. Numerous studies reported energy expenditures as one of...

Genomic regions underlying metabolic and neuronal signaling pathways are temporally consistent in a moving avian hybrid zone.

The study of hybrid zones can provide insight into the genetic basis of species differences that are relevant for the maintenance of reproductive isolation. Hybrid zones can also provide insight into climate change, species distributions, and evolution. The hybrid zone between black-capped chickadees (Poecile atricapillus) and Carolina chickadees (Poecile carolinensis) is shifting northward in response to increasing winter temperatures but is not increasing in width. This pattern indicates strong selection against chickadees with admixed genomes. Using high-resolution genomic data, we identified regions of the genomes that are outliers in both time points and do not introgress between the species; these regions may be involved in the maintenance of reproductive isolation. Genes involved in metabolic regulation processes were overrepresented in this dataset. Several gene ontology categories were also temporally consistent-including glutamate signaling, synaptic transmission, and catabolic processes-but the nucleotide variants leading to this pattern were not. Our results support recent findings that hybrids between black-capped and Carolina chickadees have higher basal metabolic rates than either parental species and suffer spatial memory and problem-solving deficits. Metabolic breakdown, as well as spatial memory and problem-solving, in hybrid chickadees may act as strong postzygotic isolation mechanisms in this moving hybrid zone.

The responses of metabolic rate and neuropeptides to food deprivation in striped hamsters (Cricetulus barabensis) with different basal metabolic rate.

High basal metabolic rate (BMR) is related to a powerful metabolic engine even under food shortage, which can lead to high levels of daily energy expenditure and requires more energy for maintenance in small mammals. To test the hypothesis that animals with different BMR levels respond differently to food shortage, we compared the changes in metabolism, morphology, and gene expression in response to food deprivation (FD) in male-striped hamsters (Cricetulus barabensis) with low (L)- or high (H)-BMR levels. After 36 hr of FD, energy expenditure, metabolic rate (MR), mass of body composition, and leptin and agouti-related peptide gene expressions in the white adipose tissues and the hypothalamus, respectively, decreased significantly in hamsters. The energy expenditure of H-BMR hamsters was reduced more than that of L-BMR hamsters after 36 hr of FD. Furthermore, MR was significantly reduced by FD, and that of the H-BMR group decreased more than that of the L-BMR group during the daytime. Therefore, our data suggest that striped hamsters with different BMR display different responses to variations in food availability. During FD, MR in H-BMR hamsters was more flexible than that in L-BMR animals and L-BMR hamsters could not reduce their MR any lower.

Functional and structural changes in aorta of mice divergently selected for basal metabolic rate

Cardiovascular diseases (CVD) are one of the most common causes of mortality likely genetically linked to the variation in basal metabolic rate (BMR). A robust test of the significance of such association may be provided by artificial selection experiments on animals selected for diversification of BMR. Here we asked whether genetically determined differences in BMR correlate with anatomical shift in endothelium structure and if so, the relaxation and contraction responses of the aorta in mice from two lines of Swiss-Webster laboratory mice (Mus musculus) divergently selected for high or low BMR (HBMR and LBMR lines, respectively). Functional and structural study of aorta showed that a selection for divergent BMR resulted in the between-line difference in diastolic aortic capacity. The relaxation was stronger in aorta of the HBMR mice, which may stem from greater flexibility of aorta mediated by higher activity of Ca2+-activated K+ channels. Structural examination also indicated that HBMR mice had significantly thicker aorta's middle layer compared to LBMR animals. Such changes may promote arterial stiffness predisposing to cardiovascular diseases. BMR-related differences in the structure and relaxation ability of aortas in studied animals may be reminiscent of potential risk factors in the development of CVD in humans.

Abstract A109: Repurposing low dose of quinoline methanol derivatives as a novel treatment for pediatric glioblastoma

Abstract Both primary brain tumors and secondary brain metastases that start in another part of the body and spreads to the brain, such as lung, breast, melanoma, kidney, nasopharynx, and colon cancers have limited or no response to chemotherapy. Through repurposing drug screen using pediatric glioblastoma cells established from newly diagnosed and recurrent patients, we identified that FDA-approved compound mefloquine have significant cancer killing properties. A growing body of evidence suggests that this extensively used anti-malaria drug may cause adverse neurological effects after crossing the blood-brain barrier and accumulates in the brain at relatively high concentration. To the amelioration of this problem, an analog campaign was conducted in selecting compounds lacking penetration but maintaining the anti-malarial properties using mefloquine as the leading compound. We therefore thought to take advantage of this unique characteristic and use low dose of these compounds and target the infiltrative disease reservoir while avoiding the neurological side effects. While this program focuses on high anti-malaria potency, low neurotoxicity (against rat neurons), and low brain absorption, we are interested in high anti-malaria potency, low general toxicity, and high brain/tumor concentration. Among these compounds, we selected TQM due to its promising results in efficacy, potency, and selectivity in killing brain tumor cells at a much lower range compared to mefloquine based on our quantitative structure-activity relationship model. Studies suggested that this group of drugs induce cell apoptosis in host and parasites through increased production of reactive oxygen species (ROS). Even though for a long time ROS is believed to promote cell proliferation; however, brain cancer cells, due to their high basal metabolic rate, are more susceptible to ROS. Inducing an increased intracellular ROS levels in brain cancer cells may trigger cell death and destroy malignant cells, while sparing normal cells. Our preliminary results confirmed that mefloquine and its derivatives induce apoptosis through autophagy and ROS signaling in brain cancer cells at a much lower concentration, and these compounds reduces tumor growth and extends animal survival in mouse models. Our results pave the way for translation of those compounds to the clinic. Citation Format: Jian Teng, Litia Carvalho, Elie Tabet, Bakhos Tannous. Repurposing low dose of quinoline methanol derivatives as a novel treatment for pediatric glioblastoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A109. doi:10.1158/1535-7163.TARG-19-A109