Metabolic Rate Research Articles

High energetic cost of color change in octopuses

For many animals, color change is a critical adaptive mechanism believed to carry a substantial energetic cost. Yet, no study to date has directly measured the energy expenditure associated with this process. We examined the metabolic cost of color change in octopuses by measuring oxygen consumption in samples of excised octopus skin during periods of chromatophore expansion and contraction and then modeled metabolic demand over the whole octopus as a function of octopus mass. The metabolic demand of the fully activated chromatophore system is nearly as great as an octopus's resting metabolic rate. This high metabolic cost carries ecological and evolutionary implications, including selective pressures in octopuses that may influence the adoption of nocturnal lifestyles, the use of dens, the reduction of the chromatophore system in deep-sea species, and metabolic trade-offs associated with foraging.

Analysis of physiological and biochemical changes and metabolic shifts during 21-Day fasting hypometabolism

This study aimed to evaluate the impact of prolonged fasting on the physiological and biochemical alterations and metabolic shifts in healthy adults and to provide experimental data and theoretical support for the hypometabolic state induced by prolonged fasting. Thirteen volunteers were selected through public recruitment to undergo a 21-day complete fasting experiment. The experimental period lasted 34 days, including a 3-day baseline, 21-day completing fasting, 5-day calorie restriction and 5-day full recovery diet. Physiological indicators such as body weight, blood pressure, blood glucose, blood ketones, and blood uric acid were evaluated along with resting metabolic rate, routine blood tests, liver function, and heart function indexes employing traditional approaches. During the 21-day complete fasting period, there was a significant decrease in body weight (average − 14.96 ± 1.55%), a reduction in blood glucose (average − 21.63 ± 0.058%), an increase in blood ketones (from baseline 0.1 ± 0.04 mmol/L to 6.61 ± 1.25 mmol/L) and blood uric acid (from baseline 385.38 ± 57.78 µmol/L to 866.31 ± 172.01 µmol/L), a continuous decline in resting energy expenditure (average − 20.3 ± 11.13%), and the respiratory quotient tending towards fat metabolism. Most of the items in the complete blood count and liver indicators remained stable and within the normal range. Heart function showed functional adaptive changes without structural damage. Prolonged fasting can reduce the body’s resting energy expenditure and adapt to body weight loss through physiological regulatory mechanisms without adverse effects on basic physiological functions or the structure of important organs. Under medical supervision, healthy adults can safely engage in prolonged fasting for up to 21 days with metabolic adaption and no damage to pivotal organ, which could provide potential technical support for human health and survival strategies in extreme conditions such as food shortages during long-duration manned spaceflight.

Exploring the impact of mitochondrial-targeting anthelmintic agents with GLUT1 inhibitor BAY-876 on breast cancer cell metabolism

BackgroundCancer cells alter their metabolic phenotypes with nutritional change. Single agent approaches targeting mitochondrial metabolism in cancer have failed due to either dose limiting off target toxicities, or lack of significant efficacy in vivo. To mitigate these clinical challenges, we investigated the potential utility of repurposing FDA approved mitochondrial targeting anthelmintic agents, niclosamide, IMD-0354 and pyrvinium pamoate, to be combined with GLUT1 inhibitor BAY-876 to enhance the inhibitory capacity of the major metabolic phenotypes exhibited by tumors.MethodsTo test this, we used breast cancer cell lines MDA-MB-231 and 4T1 which exhibit differing basal metabolic rates of glycolysis and mitochondrial respiration, respectively. Metabolic characterization was carried out using Seahorse XFe96 Bioanalyzer and statistical analysis was carried out via ANOVA.ResultsHere, we found that specific responses to mitochondrial and glycolysis targeting agents elicit responses that correlate with tested cell lines basal metabolic rates and fuel preference, highlighting the potential to cater metabolism targeting treatment regimens based on specific tumor nutrient handling. Inhibition of GLUT1 with BAY-876 potently inhibited glycolysis in both MDA-MB-231 and 4T1 cells, and niclosamide and pyrvinium pamoate perturbed mitochondrial respiration that resulted in potent compensatory glycolysis in the cell lines tested.ConclusionIn this regard, combination of BAY-876 with both mitochondrial targeting agents resulted in inhibition of compensatory glycolysis and subsequent metabolic crisis. These studies highlight targeting tumor metabolism as a combination treatment regimen that can be tailored by basal and compensatory metabolic phenotypes.

A Computational Pipeline for Identifying Gene Regulatory Networks: A Case Study of Response to Exercise.

Gene regulatory networks are foundational in the control of virtually all biological processes. These networks orchestrate a myriad of cell functions ranging from metabolic rate to the response to a drug or other intervention. The data required to accurately identify these control networks remains very cost and labor intensive typically leading to relatively sparse time course data that is largely incompatible with conventional data-driven model identification techniques. In this work, we combine empirical identification of gene-gene interactions with constraints describing the expected dynamic behavior of the network to infer regulatory dynamics from under-sampled data. We apply this to the identification of gene regulatory subnetworks recruited in groups of subjects participating in several different exercise interventions. Intervention-specific response networks are compared to one another and control actions driving differences are identified. We propose that this approach can extract statistically robust and biologically meaningful insights into gene regulatory dynamics from a dataset consisting of a small number of participants with very limited longitudinal sampling, for example pre- and post- intervention only.

The protective role of basal metabolic rate in cognitive decline: evidence from epidemiological and genetic studies.

This study aims to explore the relationship between basal metabolic rate (BMR) and cognitive impairment and assess the potential of BMR as a protective factor against cognitive decline. This investigation initially conducted a cross-sectional study of American adults from 2011 to 2014 using data from the National Health and Nutrition Examination Survey. It examined the correlation between participants' BMR and cognitive functions, exploring the association with cognitive impairment. Subsequently, publicly available genome-wide association study data was used to examine potential causal links between genetically determined BMR and specific cognitive disorders using Mendelian randomization. Cross-sectional findings revealed a significant positive correlation between higher BMR and cognitive scores. In Mendelian randomization analysis, BMR demonstrated an inverse causal relationship with Alzheimer's disease and Parkinson's dementia, suggesting BMR as a potential protective factor against these diseases. No causal links were found with vascular dementia, Lewy body dementia, and frontotemporal dementia. This study supports the role of BMR as a potential protective factor against Alzheimer's disease and Parkinson's dementia, suggesting that BMR may play an important role in preventing cognitive decline. However, due to the limitations of cross-sectional studies, further prospective studies and broader demographic samples are necessary to verify these results and explore underlying biological mechanisms. Key messages What is already known on this topic: Existing knowledge suggests a close relationship between BMR and health and cognitive functions, but detailed studies on its connection with specific cognitive impairments are still needed. What this study adds: This study found a significant positive correlation between higher BMR and cognitive improvement, potentially aiding in the prevention of Alzheimer's and Parkinson's dementia. How this study might affect research, practice, or policy: This finding guides public health strategies and personalized medicine, emphasizing the necessity for further research to validate BMR's protective effects.

ChIP-seq and structural analyses delineating the regulatory mechanism of master regulator EsrB in Edwardsiella piscicida.

As a crucial virulence regulator, EsrB possesses a LuxR-like superfamily domain at the C-terminal, which is conserved within the canonical NarL family regulators. Due to its critically important role in virulence and pathogenicity in fish hosts, the DNA binding ability has been believed to allow EsrB to regulate genes associated with the invasion process of host cells and basal metabolism in response to environmental stimuli. The lack of EsrB's crystal structure has been a major obstacle in understanding the molecular mechanisms of EsrB-DNA interaction which choreographs EsrB-mediated pathogenic behavior. Here, we conducted ChIP-seq and solved the crystal structure of the C-terminal of EsrB (EsrBC) at 2.20-Å resolution, which revealed that EsrB preferred to bind to virulence-associated promoters with a distinct 7'-4-7' pseudopalindromic DNA motif and interacted with metabolic-related promoters with a high AT DNA motif in Dulbecco's Modified Eagle's Medium (DMEM) (mimicking in vivo environments). Our results facilitate a detailed understanding of EsrB's regulatory role in Edwardsiella piscicida pathogenesis and expand our knowledge of virulence regulators in the family Hafniaceae.

Measuring energy expenditure in narcolepsy using doubly-labelled water and respiration chamber calorimetry.

Hypocretin deficiency causes type 1 narcolepsy, a condition characterised by excessive daytime sleepiness, cataplexy, and fragmented nocturnal sleep. Two-thirds of people with narcolepsy are also overweight, of which half are obese. The pathophysiology behind weight gain in people with narcolepsy remains unknown. We assessed a possible decrease in energy expenditure as a cause for overweight in narcolepsy using respiration chamber calorimetry and doubly labelled water. Ten males with type I narcolepsy and nine matched (for age, sex, and BMI) healthy controls were enrolled. Subjects stayed in a respiration chamber for 24 hours. They subsequently received doubly labelled water and wore an accelerometer for two weeks to assess energy expenditure and physical activity under daily living conditions. Total daily energy expenditure, resting energy expenditure, overnight metabolic rate, physical activity level and activity-induced energy expenditure were measured. No significant differences were found in resting energy expenditure, mean 24-hour respiration chamber energy expenditure, overnight metabolic rate and activity-induced energy expenditure when comparing people with narcolepsy type 1 to controls. Physical activity was also comparable between groups. Energy expenditure in narcolepsy type 1 is similar to matched controls, suggesting comparable metabolism and physical activity rates. It remains possible that metabolic changes are most pronounced around disease onset. In addition, patients had to discontinue their medication which may have influenced the results. Still, our findings suggest that other factors may also play a role in weight gain in narcolepsy, such as differences in dietary behaviour.

Oxidative Stress in an African Ground Squirrel, a Case of Healthy Aging and Reproduction.

Oxidative stress plays a crucial role in mediating life-history processes, where it can compromise survival and reproduction through harmful alterations to DNA, lipids, and proteins. In this study, we investigated oxidative stress in Cape ground squirrels (Xerus inauris), a longer-lived African ground squirrel species with a high reproductive skew and unique life history strategies. We measured oxidative stress as total antioxidant capacity (TAC), total oxidant status (TOS), and an oxidative stress index (OSI) in blood plasma from individuals of approximately known ages. Our results reveal a distinct pattern of decreasing oxidative stress with age, consistent across both sexes. Females exhibited lower OSI and TOS levels than males. Males employing different life-history strategies, namely natal (staying at home), had significantly lower oxidative stress compared to the band (roaming male groups), likely due to variations in metabolic rate, activity, and feeding rates. However, both strategies exhibited reduced oxidative stress with age, though the underlying mechanisms require further investigation. We propose that selection pressures favoring survival contributed to the observed reduction in oxidative stress with age, potentially maximizing lifetime reproductive success in this species.

Electrocardiographic parameters of chemically immobilized giant anteaters (Myrmecophaga tridactyla).

The giant anteater (Myrmecophaga tridactyla) is a vulnerable species that is threatened mostly due to anthropogenic pressure. The anteater is a highly specialized insectivore, challenging the species' ex situ maintenance and conservation efforts. Several dietary-associated health issues have been reported in captive anteaters, including heart conditions such as dilated cardiomyopathy. On the other hand, cardiopathy is mainly diagnosed only on necropsy, and lack of clinical reference is one of the constraints. This work describes electrocardiographic parameters in twelve zoo-kept giant anteaters (Myrmecophaga tridactyla). The giant anteaters were evaluated after chemical immobilization. Surface electrocardiography using a digital electrocardiograph was performed to acquire data on the six frontal plane leads. Four animals were placed in both left and right recumbencies to assess changes in waveforms. Nine anteaters were considered healthy and included in the statistics. The mean heart rate and electrical axis were 37.8bpm ± 3.45 and 75.6º ± 11.43, respectively. ECG parameters results were P wave duration (ms) 89.7 ± 9.2, P wave amplitude (mV) 0.14 ± 0.05, PR segment duration (ms) 148.6 ± 23, R wave amplitude (mV) 1.55 ± 0.56, QRS complex duration (ms) 88.6 ± 12.0, QT interval duration (ms) 529.6 ± 71.2, and T wave amplitude (mV) 0.76 ± 0.21. There was no difference between left or right recumbency. Heart parameters of giant anteaters are similar to other mammals and seem to be influenced both by size and metabolic rate when comparing with other species. This is the first description of ECG parameters in giant anteaters.

The mRNA N6-Methyladenosine Response to Dehydration in Xenopus laevis.

The African clawed frog, Xenopus laevis, exhibits remarkable adaptations to survive in its arid habitat, including behavioral and metabolic changes during periods of drought. During extreme dehydration, X. laevis undergoes estivation, a state characterized by increased urea and ammonia levels, depression of the metabolic rate, and tissue hypoxia. To understand the molecular mechanisms underlying these adaptations, we investigated the potential role of N6-methyladenosine (m6A), a widespread mRNA modification, in X. laevis during extreme dehydration. We analyzed the protein levels of key components in the m6A pathway, including writers (METTL3, METTL14, and WTAP), erasers (ALKBH5 and FTO), and readers (SRSF3, YTHDF1, YTHDF2, YTHDF3, and eIF3a), in the liver and kidneys of control frogs and frogs that had lost 35 ± 0.93% of their total body water. The relative protein levels generally decreased or remained unchanged, with the exception of YTHDF3, which depicted a protein level increase in the liver. Notable changes included eIF3a, which was downregulated by 26 ± 8% and 80 ± 8% in the dehydrated liver and kidney tissues, respectively. Additionally, the total m6A increased by 353 ± 30% and 177 ± 17% in dehydrated liver and kidney RNA samples, respectively. This study highlights the importance of epigenetic mechanisms in stress tolerance and provides a foundation for further exploration of the role of epigenetics in dehydration tolerance.

Commentary on Thoral et al. (2024) 'The relationship between mitochondrial respiration, resting metabolic rate and blood cell count in great tits'.

Commentary on Thoral et al. (2024) 'The relationship between mitochondrial respiration, resting metabolic rate and blood cell count in great tits'.

Near-maximally swimming schoolmaster snapper (Lutjanus apodus) have a greater metabolic capacity, and slightly lower thermal tolerance, than when tested at rest.

To assess the relationship among various measures of thermal tolerance and performance suggested for use in fish, we determined the critical thermal maximum (CTmax), critical swimming speed (Ucrit), maximum thermal tolerance while swimming [CTSmax] and realistic aerobic scope (ASR) of juvenile schoolmaster snapper (Lutjanus apodus). Their CTSmax (37.5±0.1°C) was only slightly lower than their CTmax (38.9±0.1°C) and this is probably because their maximum metabolic rate (MMR) and ASR during the former test were ∼42 and 65% higher, respectively. Furthermore, we did not observe a transition to unsteady (i.e. anaerobically fueled) swimming in the CTSmax test as we did in the Ucrit protocol. These data strongly suggest that thermal tolerance tests on fishes whose lifestyle involves schooling or sustained activity should be performed at ecologically relevant swimming speeds. Our results do not support the hypothesis that failure during a CTSmax test is due to a fish's inability to meet its tissue oxygen demands.

Response to 'Commentary on Thoral et al. (2024) The relationship between mitochondrial respiration, resting metabolic rate and blood cell count in great tits'.

Response to 'Commentary on Thoral et al. (2024) The relationship between mitochondrial respiration, resting metabolic rate and blood cell count in great tits'.

INTERACTION BETWEEN ADIPOSE TISSUE AND PHYSICAL ACTIVITY IN THE REGULATION OF BODY WEIGHT: A CONCEPTUAL NARRATIVE REVIEW

The modern obesity pandemic is characterized by difficulty in achieving and maintaining weight loss. This suggests the existence of a physiological control mechanism to maintain body mass. However, this same mechanism did not prevent obesity pandemic. The aim of this review is to explain this conundrum. Online searches of Google Scholar, PubMed, and Scopus were conducted. The main variable under physiological control is not a fixed body/fat mass but balance between energy intake and expenditure. The expenditure includes resting metabolic rate, physical activity related energy expenditure and thermic effect of food. Increased energy expenditure triggers increased energy intake to match expenditure levels and counters any weight loss. This matching of energy input and output can happen at any body/fat mass. In other words, body/fat mass can settle at any level with energy intake matched to expenditure; the so-called settling point mechanism. The particular body/fat mass settling point is determined by the availability of energy and degree of expenditure enabled by the environment. The modern environment with abundance of nutrients and motorized work has been termed obesogenic environment. It facilitates higher body mass and hence increased resting metabolic rate energy expenditure to support the increased body mass; this triggers more energy intake and thus more mass gain in a positive feedback vicious cycle. In conclusion, shifting emphasis away from body mass control to energy balance allows one to explain both the modern obesity pandemic as well as why it is so difficult to achieve and maintain weight loss.

Farmakogenomika w leczeniu zaburzeń psychicznych.

Pharmacogenomics lies at the intersection of pharmacology and genomics. It analyzes the impact of genetic variants on patient’s response to a specific drug. Pharmacogenomic tests involve the analysis of variants of genes responsible for drug metabolism, to determine the rate of drug metabolism and apply this information to clinical practice. Pharmacogenomics assists in selecting the appropriate drug and adjusting its dose to minimize side effects while maximizing the effectiveness of a drug, which accelerates the introduction of effective therapy. The prospects for its application in psychiatry are promising, although the creation of uniform recommendations is difficult due to the complexity of mental disorders and the influence of other factors, such as interactions between medications. Therefore, recommendations created by different institutions differ significantly. The aim of this article is to discuss the current possibilities of using pharmacogenomics in psychiatry and the difficulties of introducing it as a standard of psychiatric treatment.

Exploring Photoreceptor Gene Expression and Seasonal Physiology in Mediterranean Swordfish (Xiphias gladius).

Mature and immature female swordfish show different gonadal expression patterns of melatonin synthesis-related and opsin genes, indicating that seasonality affects gonadal circadian genes, especially through opsin modulation. The high energy demands of reproduction may cause mature female swordfish to become more susceptible to environmental stressors/changes, potentially affecting their health post-reproduction. The modulation of melatonin and opsin expression may also influence swordfish biology, impacting basal metabolism and stress responses. This study aimed to investigate the hepatic expression patterns of genes involved in melatonin and opsins activity after the reproductive period, comparing mature and immature females. Liver samples of swordfish females, collected from the Central Adriatic Sea, were analyzed to evaluate the expression of a melatonin receptor (mel1b), acetylserotonin O-methyltransferase (asmt), opsins (sws, VA opsin and opsin4), and stress response (sod1, sod2 and hsp4b) genes, while histological analysis focused on hepatic melanomacrophages, melanomacrophage centers, and lipid content. The expression of all genes analyzed did not differ between mature and immature females except for sws, which was significantly downregulated in mature females. The overall health conditions of mature and immature females appeared comparable, as suggested by the histological analysis and the absence of significant differences in the expression of stress response genes. Although the study used a limited number of samples and lacked a comparison between the reproductive and non-reproductive periods, the preliminary results suggest that opsins may play a role in modulating physiological processes beyond reproduction.

Reduced brain oxygen response to spreading depolarization predicts worse outcome in ischaemic stroke.

Spreading depolarization (SD) describes a propagating neuronal mass depolarization within the cerebral cortex that represents a mediator of infarct development and strongly stimulates the metabolic rate of O2 consumption. Here, we investigated the influence of Spreading Depolarization (SD) on brain tissue partial pressure of O2 (ptiO2) within the peri-infarct tissue of patients suffering malignant hemispheric stroke (MHS). This prospective observational trial included 25 patients with MHS that underwent decompressive hemicraniectomy followed by subdural placement of electrodes for electrocorticography (ECoG) and neighboring implantation of a ptiO2 probe within the peri-infarcted cortex. Continuous side-by-side ECoG + ptiO2 recordings were obtained for 3-6 days postoperatively and analyzed for the occurrence of SD-independent and SD-coupled ptiO2 changes, radiological findings, as well as their association with clinical outcome at 6 months. During the combined ECoG + ptiO2 monitoring period of 2,604 hours and among 1,022 SDs, 483 (47%) SD-coupled ptiO2 variations were identified as biphasic (59%), hypoxic (36%) or hyperoxic (5%) ptiO2 responses that differed significantly (*p<0.0001). Among the remaining 538/1,022 (53%) SDs, no SD-coupled ptiO2 response was detected, which we categorized as 'No response'. The overall infarct progression was 1.7% (IQR -2.5-10.9). Spreading Depolarization characteristics regarding type, duration and frequency, as well as SD-independent baseline ptiO2 had no association with outcome. In contrast, a high occurrence rate and amplitude of SD-coupled variations in ptiO2 were associated with improved outcome at 6 months (occurrence: r=-0.62, *p=0.035; amplitude: r=-0.57, *p=0.024; Spearman correlation). In conclusion, an absent or reduced ptiO2 response to SD could indicate tissue-at-risk and help direct targeted treatment strategies in ischemic stroke, which is further evidence that not all SDs are the same, but that tissue responses coupled to SD such as ptiO2 contain prognostic information. In particular, a lack of SD-coupled ptiO2 variations appears to be a predictor of worse outcome in large hemispheric stroke.

EGFR Evalutation among the Hypothyroid Patients Attending at a Tertiary Center of Chattogram

Background: Hypothyroidism is a prevalent endocrine illness that affects people all over the world. The modulation of renal hemodynamics and basal metabolic rate is disrupted in hypothyroidism. The kidney is generally involved in thyroid hormone metabolism, breakdown and excretion. Chronic renal hypoperfusion affects the hypothalamic pituitary-thyroid axis, resulting in low circulating thyroid hormone levels, changed peripheral hormone metabolism, decreased tissue thyroid hormone content and altered thyroid iodine storage. Recent research has linked an increased risk of hypothyroidism to a decreased estimated Glomerular Filtration Rate (eGFR). The purpose of the study is to determine the association between eGFR with hypothyroidism in a tertiary care hospital of Chattogram. Materials and methods: A cross-sectional study was done during July 2022 to June 2023 including 100 diagnosed hypothyroidism cases attending in Chittagong Medical College Hospital. Serum Thyroid Stimulating Hormone (TSH) serum free thyroxine (FT4) serum creatinine, and blood urea were measured. The estimated glomerular filtration rate (eGFR) were determined. The result were analysed using SPSS version 25. Results: The mean age was 42.76±10.18 years with 93% female. Most of the patients (92%) were in a subclinical hypothyroid state and 8% were in an overt hypothyroid state. The mean ±SD serum creatinine levels and urea levels were 0.8±0.2mg/dl and 25.4±6.5 mg/dl, respectively. The mean eGFR was 75.36±7.54 ml/min/1.73 m2. There was a significant decrease in mean eGFR in the &lt; 60 ml/min/1.73m2 group among the study population. There was a significant association between decreased eGFR and hypothyroidism. Serum TSH had significantly shown a negative correlation with eGFR. Serum TSH level had a significant positive correlation with serum creatinine (r=0.56, p&lt;0.05) and serum urea (r=0.25, p&lt;0.05). There was a significant eGFR difference between subclinical hypothyroidism and overt hypothyroidism. Conclusion: It can be concluded from this study that the hypothyroidism was significantly correlated with decreased eGFR. IAHS Medical Journal Vol 7(1), June 2024; 86-90

Influence of pharmacotherapy on function of biotransformation of xenobiotics liver in patients with neuropsychiatric disorders

BACKGROUND: The mechanisms of drug interactions of psychotropic drugs are associated with the processes of drug biotransformation by enzymes of microsomal oxidation of cytochrome P-450 in the liver. Various drugs can increase or decrease the activity of enzymes of the cytochrome P450-dependent system. AIM: To evaluate the effect of pharmacotherapy with psychotropic drugs: alprazolam, bromazepam, lithium carbonate on the metabolic rate of the model substrate antipyrine in saliva in patients with neuropsychiatric disorders; the effect of the enzyme-inducing activity of the original anticonvulsant 1-[(3-chlorophenyl)(phenyl)methyl]urea on the pharmacokinetic parameters of antipyrine in healthy volunteers. MATERIALS AND METHODS: 34 male patients were divided into three groups according to the nosological forms of diseases according to ICD-10: Group 1 — heading F43.23 and F43.25; 2 — F06.61; 3 — F41.2. Patients in the group 1 were prescribed alprazolam, in the 2 — bromazepam, in the 3 — lithium carbonate, for a course of 21 days. The comparison group consisted of 10 healthy volunteers. The original anticonvulsant was prescribed to the volunteers. Determination of the pharmacokinetics of antipyrine parameters as a test witness of the processes of elimination from the body was carried out in saliva before and after the end of therapy at a dose of 10 mg/kg once. RESULTS: Alprazolam administration by patients of group 1 at a dose of 0.5–1.5 mg/day for 21 days did not significantly affect the pharmacokinetic parameters of antipyrine: T1/2, Clt, AUC. Alprazolam did not change the elimination of antipyrine from the saliva of patients. In patients of the group2, who received bromazepam at a dose of 6–12 mg / day,a background decrease in T1/2, an increase in Clt, a decrease in AUC due to concomitant therapy were noted. Comparison of the pharmacokinetic parameters of antipyrine under the influence of bromazepam with background values not reveal significant differences. Therapy with lithium carbonate at a dose of 500–1000 mg/day in patients of the group 3 did not change the parameters of antipyrine elimination. The obtained data indicate that the drugs do not affect the activity of liver microsomal oxidation in patients. The study of the effect of 1-[(3-chlorophenyl)(phenyl)methyl]urea on the pharmacokinetic parameters of antipyrine in volunteers revealed a diametrically opposite result: a significant decrease in T1/2 by 2 times, an increase in Clt and a decrease in AUC, which indicates accelerated elimination of antipyrine from the saliva of the subjects and indicates the induction of liver microsomal oxidation. CONCLUSIONS: Pharmacotherapy using the studied psychotropic drugs in patients is not associated with the induction or inhibition of liver enzymes, which indicates the absence of drug pharmacokinetic interference. The original anticonvulsant 1-[(3-chlorophenyl)(phenyl)methyl]urea stimulated the induction of liver microsomal oxidation in volunteers.

Analysis of Lipid Metabolism in Adipose Tissue and Liver of Chinese Soft-Shelled Turtle Pelodiscus sinensis During Hibernation.

Hibernation serves as an energy-conserving strategy that enables animals to withstand harsh environments by reducing their metabolic rate significantly. However, the mechanisms underlying energy adaptation in hibernating ectotherms, such as Pelodiscus sinensis, remain contentious. This paper first reports the decrease in lipid levels and the expression of metabolism-related genes in P. sinensis during hibernation. The results of physiological and biochemical analysis showed that adipocyte cell size was reduced and liver lipid droplet (LD) contents were decreased during hibernation in P. sinensis. Concurrently, serum levels of triglycerides (TGs), total cholesterol (TC), non-esterified fatty acids (NEFAs), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) were diminished (n = 8, p < 0.01), while an increase in serum glucose (Glu) (n = 8, p < 0.01) was noted among hibernating P. sinensis. These observations suggest a shift in energy metabolism during hibernation. To gain insights into the molecular mechanisms, we performed integrated transcriptomic and lipidomic analyses of adipose tissue and livers from summer-active versus overwintering P. sinensis, which revealed downregulation of free fatty acids (FFAs), triglycerides (TGs), diglycerides (DGs), and ceramides (Cers) during hibernation. The results of GSEA analysis showed that metabolic pathways associated with lipid metabolism, including glycerolipid metabolism and regulation of lipolysis in adipocytes, were suppressed significantly. Notably, acute cold exposure induced significant downregulation of genes related to lipolysis such as PNPLA2, ABHD5, LPL, CPT1A, and PPARα. The results indicate that lipolysis is suppressed during hibernation in P. sinensis. Collectively, these findings deepen our understanding of survival mechanisms and elucidate the unique energy adaptation strategies employed by hibernating ectotherms. Future research should explore the implications of these findings for the conservation of ectotherms and the applications for artificially inducing hibernation.