Differences in the range of thermoneutral zone between mouse strains: potential effects on translational research.

Laboratory mice are commonly used for studies emulating human metabolism. To render human energetics, their ratio of daily (DEE) to basal (BMR) energy expenditure of 1.7-1.8 should be maintained. However, the DEE/BMR ratio strongly depends on whether a given study using a mouse model is carried out above, or below the lower critical temperature (LCT) of the thermoneutral zone, which is rarely considered in translational research. Here, we used mice artificially selected for high or low rates of BMR along with literature data to analyze the effect of ambient temperature on possible systematic bias in DEE/BMR. We demonstrated that the estimated LCTs of mice from the high and low BMR lines differ by more than 7°C. Furthermore, the range of variation of LCTs of mouse strains used in translational research spans from 23 to 33°C. Differences between LCTs in our selected mice and other mouse strains are mirrored by differences in their DEE-to-BMR ratio, on average increasing it at the rate of 0.172°C-1 at temperatures below LCT. Given the wide range of LCTs in different mouse strains, we conclude that the energetic cost of thermoregulation may differ greatly for different mouse strains with a potentially large impact on translational outcomes. Thus, the LCT of a given mouse strain is an important factor that must be considered in designing translational studies.

Phenotypic flexibility in metabolic adjustments and digestive function in white-shouldered starlings: responses to short-term temperature acclimation.

Changing the intrinsic rate of metabolic heat production is the main adaptive strategy for small birds to cope with different ambient temperatures. In this study, we tested the hypothesis that the small passerine the white-shouldered starling (Sturnus sinensis) can modulate basal metabolism under temperature acclimation by changing the morphological, physiological and biochemical state of its tissues and organs. We measured the effects of temperature on body mass, basal metabolic rate (BMR), wet mass of various internal organs, state 4 respiration (S4R) and cytochrome c oxidase (CCO) activity in the pectoral muscle and organs, metabolites in the pectoral muscle, energy intake, histological dynamics and the activity of duodenal digestive enzymes. Warm acclimation decreased BMR to a greater extent than cold acclimation. At the organ level, birds in the cold-acclimated group had significantly heavier intestines but significantly lighter pectoral muscles. At the cellular level, birds in the cold-acclimated group showed significantly higher S4R in the liver and heart and CCO activity in the liver and kidney at both the mass-specific and whole-organ levels. A metabolomic analysis of the pectoral tissue revealed significantly higher lipid decomposition, amino acid degradation, ATP hydrolysis, and GTP and biotin synthesis in cold-acclimated birds. Acclimation to cold significantly increased the gross energy intake (GEI), feces energy (FE) and digestive energy intake (DEI) but significantly decreased the digestive efficiency of these birds. Furthermore, cold-acclimated birds had a higher maltase activity and longer villi in the duodenum. Taken together, these data show that white-shouldered starlings exhibit high phenotypic flexibility in metabolic adjustments and digestive function under temperature acclimation, consistent with the notion that small birds cope with the energy challenges presented by a cold environment by modulating tissue function in a way that would affect BMR.

Basal metabolic rate and the risk of urolithiasis: a two-sample Mendelian randomization study.

OBJECTIVE: Few studies have investigated the impact of basal metabolic rate (BMR) on the development of urolithiasis, and the causal relationship is yet to be established. In this study, a two-sample Mendelian randomization (MR) analysis was utilized to identify the causal relationship between BMR and risk of urolithiasis. METHOD: Genetic instruments for BMR were drawn from a public genome-wide association study (GWAS). Summary dates on BMR and urolithiasis were obtained from a GWAS meta-analysis with sample sizes of 454,874 and 212,453, respectively. The inverse-variance weighted (IVW) method was provided as the main approach to estimate the causal relationship. The weighted-median method and the MR-Egger method were used as supplements to the IVW method. In addition, we conducted sensitivity analyses, including heterogeneity tests, pleiotropy tests and leave-one-out analysis, to assess the robustness of the outcomes. Furthermore, the funnel plot asymmetry was visually inspected to evaluate possible bias. RESULTS: The inverse-variance weighted data revealed that genetically predicted BMR significantly decreased the risk of urolithiasis [beta coefficient (beta): - 0.2366, odds ratio (OR): 0.7893, 95% confidence interval (CI) 0.6504-0.9579, p = 0.0166]. CONCLUSIONS: BMR has causal effects on urolithiasis in an MR study, and the risk of urolithiasis in patients with lower levels of BMR is higher.

Causal relationship between basal metabolic rate and intervertebral disc degeneration: a Mendelian randomization study.

BACKGROUND: The role of basal metabolic rate (BMR) in intervertebral disc degeneration (IVDD) is still uncertain. To address this gap, we conducted a Mendelian randomization (MR) study to comprehensively explore the causal relationship between BMR and IVDD. METHODS: BMR data were obtained from a large genome-wide association study (GWAS) database, while IVDD data were derived from the FinnGen project. The causal relationship between IVDD and BMR was investigated using MR, with inverse-variance weighting (IVW) as the primary estimate. MR-Egger weighed median and weighed mode were employed for robustness. Sensitivity analyses, including the Cochran Q test, leave-one-out analysis, and MR-Egger intercept analysis, were conducted. Furthermore, the study also identified causal relationships between IVDD and factors associated with BMR (hyperthyroidism, type 2 diabetes, standing height, weight, and body mass index). Multivariable MR was applied to further assess the direct effect of BMR on IVDD. RESULTS: Genetic predisposition to BMR (after removing outliers OR: 1.49; 95% CI: 1.37-1.63; P = 5.073e-21) were associated with an increased risk of IVDD. Additionally, IVDD risk increased with greater height, weight, and BMI. No causal relationship was observed between hy/thy and T2D and intervertebral disc degeneration (IVDD) (P > 0.05). In multivariable MR, a significant causal association between BMR and IVDD persisted, even after adjusting for BMI, height, and weight. CONCLUSION: In this study, we successfully identified that a higher BMR is independently and causally linked to IVDD, indicating an increased risk of developing IVDD. These findings suggest that managing BMR could potentially mitigate the risk of IVDD.

Effect of basal metabolic rate on rheumatoid arthritis: a Mendelian randomization study.

PURPOSE: Basal metabolic rate (BMR) as one of the most basic and significant indicators of metabolism has been associated with human health. Previous studies showed that the development of rheumatoid arthritis (RA) is linked to BMR; however, the causal relationship between BMR and RA is unknown. Thus, we aimed to explore the causal relationship between BMR and RA as well as RA-related factors. METHODS: Mendelian randomization (MR) analysis was performed on collected genome-wide association studies information. The effect of horizontal pleiotropy was detected by MR-PRESSO and MR-Radial. Five MR analysis methods were applied, including inverse variance weighted, MR-Egger, weighted median, weighted mode, and simple mode. Four sensitivity analysis methods were used for the validation of the significant MR analysis results. A two-component mixture of regressions method was additionally used to validate single nucleotide polymorphisms and to verify results. RESULTS: Genetically, there is a causal effect of BMR on overall RA (odds ratio = 1.25, 95% confidence interval: 1.07-1.47, PIVW = .006), seropositive RA (odds ratio = 1.20, 95% confidence interval: 1.01-1.44, PIVW = .035), and seronegative RA (odds ratio = 1.36, 95% confidence interval: 1.04-1.78, PIVW = .023). Sensitivity analyses validated the robustness of the above associations. No evidence supported the effect of RA on BMR. Moreover, BMR showed no causal relationship with rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, interleukin-1ß, tumor necrosis factor-α, and matrix metallopeptidase 3. CONCLUSION: MR results implied the causal effect of BMR on RA and raised our attention to the importance of BMR in RA's pathology.

[Bioimpedance analysis of body composition and rest energy expenditure in highly trained cross-country skiers].

The body composition monitoring using bioimpedance analysis (BIA) is important in assessing the functional state of athletes in sports. Based on changes of body composition, it is possible to optimize the actual dietary intake, as well as successfully organize the training process. The purpose of this research was to conduct a comparative assessment of BIA parameters and rest energy expenditure (REE) in highly trained cross-country skiers and young non-athletes. Material and methods. The members of the national cross-country skiing team from the Komi Republic and Russian Federation (n=30; age - 22.3±2.7 years) were examined. Practically healthy medical students served as a control group for the present study (n=40; age - 20.2±2.4 years). The participants successively passed the following study steps: assessment of the body composition by BIA (ACCUNIQ BC380), REE determination by indirect non-fasting calorimetry and calculation technique. Results. The parameters of total body water, fat-free mass, lean tissue and body cell mass were higher in contrast to the fat mass percentage in the athletes (р<0.001). The calculated REE was lower than measured REE among all the participants. At the same time, the REE calculated by the Ketch-McArdle formula significantly differed between the groups, while no differences were found between the REE calculated by the Harris-Benedict prediction equation. The measured REE were significantly higher by 16% (p<0.001) i n athletes compared to those in the control group. Conclusion. The body composition of athletes was distinguished by a significantly higher amounts of total body water, fat-free mass, skeletal muscle, active cell mass, and lower percentage of fat mass compared to healthy untrained individuals. The results obtained among athletes coincided with the idea that the magnitude of REE is determined by the mass of metabolically active tissues and to a lesser extent depends on the fat mass. BIA results can be used to monitor athletes' body composition during the training process.

Insight into the causality between basal metabolic rate and endometrial and ovarian cancers: Analysis utilizing systematic Mendelian randomization and genetic association data from over 331,000 UK biobank participants.

BACKGROUND: Observational studies have demonstrated that basal metabolic rate (BMR) is associated with the risk of endometrial cancer (EC) and ovarian cancer (OC). However, it is unclear whether these associations reflect a causal relationship. OBJECTIVE: To reveal the causality between BMR and EC and OC, we performed the first comprehensive two-sample Mendelian randomization (MR) analyses. METHODS: Genetic variants were used as proxies of BMR. GWAS summary statistics of BMR, EC and OC were obtained from the UK Biobank Consortium, Endometrial Cancer Association Consortium and Ovarian Cancer Association Consortium respectively. The inverse variance weighted method was employed as the main approach for MR analysis. A series of sensitivity analyses were implemented to validate the robustness and reliability of the results. RESULTS: BMR was significantly related to an increased risk of EC (ORSD  = 1.49; 95% CI: 1.29-1.72; p-Value < .001) and OC (ORSD  = 1.21; 95% CI: 1.08-1.35; p-Value < .001). Furthermore, the stratified analysis indicated that BMR was positively associated with endometrioid endometrial cancer (EEC) (ORSD  = 1.45; 95% CI, 1.23-1.70; p-Value < .001), clear cell ovarian cancer(CCOC) (ORSD  = 1.89; 95% CI:1.35-2.64; p-Value < .001) and endometrioid ovarian cancer risk (EOC) (ORSD  = 1.45; 95% CI: 1.12-1.88; p-Value = .005). However, there were no significant associations of BMR with invasive mucinous ovarian cancer (IMOC), high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC). The robustness of the above results was further verified in sensitivity analyses. CONCLUSION: The MR study provided etiological evidence for the positive association of BMR with the risk of EC, EEC, OC, CCOC and EOC. But this study did not provide enough evidence suggesting the causal associations of BMR with IMOC, HGSOC and LGSOC.

Spatial variation in the evolutionary potential and constraints of basal metabolic rate and body mass in a wild bird.

An organism's energy budget is strongly related to resource consumption, performance, and fitness. Hence, understanding the evolution of key energetic traits, such as basal metabolic rate (BMR), in natural populations is central for understanding life-history evolution and ecological processes. Here we used quantitative genetic analyses to study evolutionary potential of BMR in two insular populations of the house sparrow (Passer domesticus). We obtained measurements of BMR and body mass (Mb ) from 911 house sparrows on the islands of Leka and Vega along the coast of Norway. These two populations were the source populations for translocations to create an additional third, admixed 'common garden' population in 2012. With the use of a novel genetic group animal model concomitant with a genetically determined pedigree, we differentiate genetic and environmental sources of variation, thereby providing insight into the effects of spatial population structure on evolutionary potential. We found that the evolutionary potential of BMR was similar in the two source populations, whereas the Vega population had a somewhat higher evolutionary potential of Mb than the Leka population. BMR was genetically correlated with Mb in both populations, and the conditional evolutionary potential of BMR (independent of body mass) was 41% (Leka) and 53% (Vega) lower than unconditional estimates. Overall, our results show that there is potential for BMR to evolve independently of Mb , but that selection on BMR and/or Mb may have different evolutionary consequences in different populations of the same species.

Selective breeding for high voluntary exercise in mice increases maximal (V̇O2,max) but not basal metabolic rate.

In general, sustained high rates of physical activity require a high maximal aerobic capacity (V̇O2,max), which may also necessitate a high basal aerobic metabolism (BMR), given that the two metabolic states are linked via shared organ systems, cellular properties and metabolic pathways. We tested the hypotheses that (a) selective breeding for high voluntary exercise in mice would elevate both V̇O2,max and BMR, and (b) these increases are accompanied by increases in the size of some internal organs (ventricle, triceps surae muscle, liver, kidney, spleen, lung, brain). We measured 72 females from generations 88 and 96 of an ongoing artificial selection experiment comprising four replicate High Runner (HR) lines bred for voluntary daily wheel-running distance and four non-selected control lines. With body mass as a covariate, HR lines as a group had significantly higher V̇O2,max (+13.6%, P<0.0001), consistent with previous studies, but BMR did not significantly differ between HR and control lines (+6.5%, P=0.181). Additionally, HR mice did not statistically differ from control mice for whole-body lean or fat mass, or for the mass of any organ collected (with body mass as a covariate). Finally, mass-independent V̇O2,max and BMR were uncorrelated (r=0.073, P=0.552) and the only statistically significant correlation with an organ mass was for V̇O2,max and ventricle mass (r=0.285, P=0.015). Overall, our results indicate that selection for a behavioral trait can yield large changes in behavior without proportional modifications to underlying morphological or physiological traits.

Seasonal variation in thermoregulatory capacity of three closely related Afrotropical Estrildid finches introduced to Europe.

A species' potential geographical range is largely determined by how the species responds physiologically to its changing environment. It is therefore crucial to study the physiological mechanisms that species use to maintain their homeothermy in order to address biodiversity conservation challenges, such as the success of invasions of introduced species. The common waxbill Estrilda astrild, the orange-cheeked waxbill E. melpoda, and the black-rumped waxbill E. troglodytes are small Afrotropical passerines that have established invasive populations in regions where the climate is colder than in their native ranges. As a result, they are highly suitable species for studying potential mechanisms for coping with a colder and more variable climate. Here, we investigated the magnitude and direction of seasonal variation in their thermoregulatory traits, such as basal (BMR), summit (Msum) metabolic rates and thermal conductance. We found that, from summer to autumn, their ability to resist colder temperatures increased. This was not related to larger body masses or higher BMR and Msum, but instead, species downregulated BMR and Msum toward the colder season, suggesting energy conservation mechanisms to increase winter survival. BMR and Msum were most strongly correlated with temperature variation in the week preceding the measurements. Common waxbill and black-rumped waxbill, whose native ranges encompass the highest degree of seasonality, showed the most flexibility in metabolic rates (i.e., stronger downregulation toward colder seasons). This ability to adjust thermoregulatory traits, combined with increased cold tolerance, may facilitate their establishment in areas characterized by colder winters and less predictable climates.

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.

Seasonal adjustments in body mass and basal thermogenesis in Chinese hwameis (Garrulax canorus): the roles of temperature and photoperiod.

For small birds to survive during seasonal acclimatization in temperate zones, regulation of body mass and thermogenesis is crucial. To determine the role of temperature and photoperiod in seasonal changes in body mass and thermogenesis in Chinese hwameis (Garrulax canorus), we compared body mass, basal metabolic rate (BMR), energy intake and cellular metabolic capacity of the tissue (muscle) and/or organs (liver, kidney, heart and small intestine) in seasonally acclimatized and laboratory-acclimated hwameis. A significant seasonal influence on body mass and BMR (which peaked in winter) was found, and these variations were mirrored by exposing the housed birds to cold temperatures or a short photoperiod. The level of dry matter intake, gross energy intake and digestible energy intake was higher during winter, and in housed animals that were exposed to cold temperatures. These results suggest that by increasing energy intake and thermogenesis, Chinese hwameis can overcome winter thermoregulatory challenges. When compared with warm-acclimated birds, cold-acclimated birds displayed higher mass-specific and whole-organ state 4 respiration in the muscle, liver and kidney, and higher mass-specific and whole-organ cytochrome c oxidase activity in the liver. These data demonstrate that cellular thermogenesis partly underpins basal thermoregulation in Chinese hwameis. Cold temperature and short photoperiod can be used as helpful environmental cues during seasonal acclimatization. However, the role of temperature is more significant compared with that of photoperiod in Chinese hwameis; the changes in energy metabolism and thermoregulation induced by temperature appear to be intensified by photoperiod.

Energetic dissociation of individual and species ranges.

The use of energy is universal to all life forms and all levels of biological organization, potentially linking processes operating at variable scales. Individual and species ranges might be energetically constrained, yet divergent metabolic limitations at both scales can disassociate these individual and species traits. We analysed comparative energetic and range data to unravel the mechanistic basis of the dissociation between individual and species range sizes observed among mammalian species. Our results demonstrate that basal, or maintenance, metabolism negatively correlates with individual ranges, but, at the same time, it positively correlates with species ranges. High aerobic capacity, i.e. maximum metabolic rate, positively correlates with individual ranges, but it is weakly related to species range size. These antagonistic energetic constraints on both ranges could lead to a disassociation between individual and species traits and to a low covariation between home and species range sizes. We show that important organismal functions, such as basal and maximum metabolic rates, have the potential to unravel mechanisms operating at different levels of biological organization and to expose links between energy-dependent processes at different scales.

No evidence of metabolic costs following adaptive immune activation or reactivation in house sparrows.

The energy cost of adaptive immune activation in endotherms is typically quantified from changes in resting metabolic rate following exposure to a novel antigen. An implicit assumption of this technique is that all variation in energy costs following antigenic challenge is due solely to adaptive immunity, while ignoring potential changes in the energy demands of ongoing bodily functions. We critically assess this assumption by measuring both basal metabolic rate (BMR) and exercise-induced maximal metabolic rate (MMR) in house sparrows before and after the primary and two subsequent vaccinations with either saline (sham) or two novel antigens (keyhole limpet haemocyanin and sheep red blood cells; KLH and SRBC, respectively). We also examined the effect of inducing male breeding levels of testosterone (T) on immune responses and their metabolic costs in both males and females. Although there was a moderate decrease in KLH antibody formation in T-treated birds, there was no effect of T on BMR, MMR or immunity to SRBC. There was no effect of vaccination on BMR but, surprisingly, all vaccinated birds maintained MMR better than sham-treated birds as the experiment progressed. Our findings caution against emphasizing energy costs or nutrient diversion as being responsible for reported fitness reductions following activation of adaptive immunity.

Prehatching temperatures drive inter-annual cohort differences in great tit metabolism.

Basal metabolic rate (BMR) constitutes the lowest metabolic rate in a resting animal and is, therefore, considered to reflect the energetic cost of maintenance in endotherms. BMR is a reversible plastic trait that changes with environmental and ecological circumstances, albeit being heritable and susceptible to selection. Inter-individual variation within populations of small birds is substantial, and while many of the drivers of such variation have been identified, many remain unexplained. We studied winter BMR variation of juveniles over a 15-year period in a wild population of great tits Parus major at the northern border of their distribution. BMR during winter consistently changed between years, even after controlling for environmental factors, suggestive of a non-reversible developmental plasticity shaping the adult metabolic phenotype. BMR in cohorts of wintering great tits varied among winters as a response to minimum ambient temperatures experienced early in life, during the prehatching period. This developmental plasticity might be adaptive if temperatures experienced by growing embryos would metabolically prime them to an environment that they will likely encounter in future life. However, in line with a more unpredictable future climate, the risk of phenotype-environment mismatch is likely to lead to certain cohorts being poorly adapted to prevailing winter conditions, resulting in wider annual fluctuations in population size.

Interaction of MC4R rs17782313 variants and dietary carbohydrate quantity and quality on basal metabolic rate and general and central obesity in overweight/obese women: a cross-sectional study.

BACKGROUND: Recent studies have shown that dietary carbohydrate quantity and quality as well as genetic variants may contribute to determining the metabolic rate and general and central obesity. This study aimed to examine interactions between melanocortin 4 receptor gene (MC4R) rs17782313 and dietary carbohydrate intake, glycemic index (GI), and glycemic load (GL) on body mass index (BMI), waist circumferences (WC), basal metabolic rate (BMR), and BMR/kg in overweight/obese women. METHODS: A total of 282 Iranian women (BMI ≥ 25) aged 18-56 years were enrolled in this cross-sectional study. All participants were assessed for blood parameters, body composition, BMR, and dietary intake. Dietary carbohydrate intake, GI, and GL were determined using a valid, reliable 147-item food frequency questionnaire. MC4R rs17782313 was genotyped by the restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: After adjustment for age and energy intake, significant interactions were observed between carbohydrate intake and MC4R rs17782313 in terms of BMI (P Interaction = 0.007), WC (P Interaction = 0.02), and BMR/kg (P Interaction = 0.003) in this way that higher carbohydrate intake, compared with lower intake, was associated with an increase in BMI and WC for individuals with C allele carriers (TC + CC genotypes), while related to an increase in BMR/kg for those carrying the TT genotype. No significant interaction was found between MC4R rs17782313 and GI and GL on BMI, WC, BMR/kg, and BMR. CONCLUSIONS: Interactions between the MC4R rs17782313 and carbohydrate intake probably can have an effect on BMI, WC, and BMR/kg in overweight/obese women.

Resting energy expenditure in Parkinson's disease patients under dopaminergic treatment.

Background: Weight homeostasis is complex in Parkinson's disease (PD) and body weight changes substantially throughout the course of the disease. We designed a case-control study to (i) investigate whether PD is associated with changes in resting energy expenditure (REE), (ii) to assess how accurately REE could be predicted for individuals with PD utilizing the equations constructed for healthy individuals, and (iii) to eventually construct a new equation.Materials & Methods: Measured REE (mREE) was compared between 122 PD patients and 122 gender and body mass index (BMI)-matched controls. The accuracy of estimated REE by 5 common equations (Harris/Benedict-1919, Roza/Shizgal-1984, Mifflin St. Jeor, WHO/FAO and aggregate formula) was investigated in PD using Bland-Altman analysis and reported as the frequency of accurate predictions (±10%). Concordance correlation coefficients (CCC) were also calculated. Then, we regressed a new REE equation - using gender, age, weight, height and Hoehn-Yahr stage - and validated it in an independent sample (N = 100).Results: No significant difference in mREE was recorded between the whole PD sample and healthy controls. However, mREE was increased in patients with BMI ≥ 30 kg/m2 and Hoehn-Yahr stage ≥ 3. Limited accuracy was present in the available REE equations (accurate prediction [±10%] frequency, <60% for all). For the new equation, the proportion of accurate prediction was 67.0% (overestimation, 24.0%) and CCC was 0.77.Conclusion: PD patients are not commonly characterized by an increase in REE. This is limited to patients suffering from obesity and more severe disease. Common REE equations appear to be inaccurate. The new predictive equation proposed in this study provided better REE estimates.

The lower basal metabolic rate is associated with increased risk of osteosarcopenia in postmenopausal women.

BACKGROUND: The goal of this study is to clarify clinical, functional, and biochemical features of postmenopausal women who are at risk of developing osteosarcopenia. METHODS: This is a cross-sectional study undertaken to investigate the co-accordance of osteoporosis and sarcopenia and common risk factors on 305 postmenopausal Iranian women. Sarcopenia and osteoporosis were defined based on the European Working Group on sarcopenia in Older People guidelines and WHO criteria, respectively. Confounding factors including age, menopausal age, obesity, sun exposure, physical activity, macronutrient composition, and calcium and vitamin D supplementations were considered for all participants. A multivariate model was used to consider the common risk factors of both disorders; osteoporosis and sarcopenia. RESULTS: The mean age was 57.9 years ± 6.0 SD (range: 48-78 years) and 37.4% of patients were 60 years or older. Among all participants, 35.7% were obese (BMI ≥ 30 kg/m2). Approximately 45% of all the study population had insufficient physical activity and at least half of participants had insufficient intake of protein. There was a significant correlation between bone density and muscle mass and basal metabolic rate (BMR) (p < 0.01). In multivariate-multivariable regression model, after Bonferroni correction for obesity, lower BMR was the only one associated with both lower muscle mass and bone density in lumbar and hip sites (p < 0.007). CONCLUSIONS: Our data suggest that low BMR might be an early predictor for concordance of osteoporosis and sarcopenia in postmenopausal women.

Basal metabolic rate and risk of multiple sclerosis: a Mendelian randomization study.

To determine the relationship between basal metabolic rate (BMR) and multiple sclerosis (MS) susceptibility, we analyzed genome-wide association study (GWAS) summary statistics data from the International Multiple Sclerosis Genetics Consortium on a total of 115,803 participants of European descent, including 47,429 patients with MS and 68,374 controls. We selected 378 independent genetic variants strongly associated with BMR in a GWAS involving 454,874 participants as instrumental variables to examine a potential causal relationship between BMR and MS. A genetically predicted higher BMR was associated with a greater risk of MS (odds ratio [OR]: 1.283 per one standard deviation increase in BMR, 95% confidence interval [CI]: 1.108-1.486, P = 0.001). Moreover, we used the lasso method to eliminate heterogeneity (Q statistic = 384.58, P = 0.370). There was no pleiotropy in our study and no bias was found in the sensitivity analysis using the leave-one-out test. We provide novel evidence that a higher BMR is an independent causal risk factor in the development of MS. Further work is warranted to elucidate the potential mechanisms.

Linc-RAM is a metabolic regulator maintaining whole-body energy homeostasis in mice.

Long noncoding RNAs (lncRNAs) are known to have profound functions in regulating cell fate specification, cell differentiation, organogenesis, and disease, but their physiological roles in controlling cellular metabolism and whole-body metabolic homeostasis are less well understood. We previously identified a skeletal muscle-specific long intergenic noncoding RNA (linc-RNA) activator of myogenesis, Linc-RAM, which enhances muscle cell differentiation during development and regeneration. Here, we report that Linc-RAM exerts a physiological function in regulating skeletal muscle metabolism and the basal metabolic rate to maintain whole-body metabolic homeostasis. We first demonstrate that Linc-RAM is preferentially expressed in type-II enriched glycolytic myofibers, in which its level is more than 60-fold higher compared to that in differentiated myotubes. Consistently, genetic deletion of the Linc-RAM gene in mice increases the expression levels of genes encoding oxidative fiber versions of myosin heavy chains and decreases those of genes encoding rate-limiting enzymes for glycolytic metabolism. Physiologically, Linc-RAM-knockout mice exhibit a higher basal metabolic rate, elevated insulin sensitivity and reduced fat deposition compared to their wild-type littermates. Together, our findings indicate that Linc-RAM is a metabolic regulator of skeletal muscle metabolism and may represent a potential pharmaceutical target for preventing and/or treating metabolic diseases, including obesity.