Sexual Dimorphism in Energy Metabolism of Wistar Rats Using Data Analysis

Leškaničová, Andrea; Chovancova, Olga; Babinčák, Marián; Verbóová, Ľudmila; Benetinová, Zuzana; Maceková, Denisa; Kostolny, Jozef; Smajda, B; Kisková, Terézia

doi:10.3390/molecules25102353

Cited by 18 publications

(12 citation statements)

References 35 publications

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“…This was surprising given that the requirements for egg production in females should lead to marked different metabolic requirements in the liver. Our findings are in good agreement with published data, reporting sex-specific differences in metabolite patterns in rodents [21][22][23], humans [24] and also medaka, the latter using a multi-omics approach [18].…”

Section: Discussionsupporting

confidence: 93%

Strain-Specific Liver Metabolite Profiles in Medaka

2021

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The relationship between genetic variation and phenotypic traits is often poorly understood since specific genotypes do not always easily translate into associated phenotypes, especially for complex disorders. The genetic background has been shown to affect metabolic pathways and thus contribute to variations in the metabolome. Here, we tested the suitability of NMR metabolomics for comparative analysis of fish lines as a first step towards phenotype-genotype association studies. The Japanese rice fish, medaka (Oryzias latipes), is a widely used genetic vertebrate model with several isogenic inbred laboratory strains. We used liver extracts of medaka iCab and HO5 strains as a paradigm to test the feasibility of distinguishing the metabolome of two different inbred strains. Fifteen metabolites could be detected in uni- and multivariate analyses that showed strain-specific levels. Differences could be assigned to specific metabolic pathways. Our results show that NMR spectroscopy is a suitable method to detect variance of the metabolome caused by subtle genetic differences. Thus, it has the potential to address genotype–phenotype associations in medaka, providing an additional level of phenotypic analysis.

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Section: Discussionsupporting

confidence: 93%

Strain-Specific Liver Metabolite Profiles in Medaka

2021

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“…Sex differences in metabolism/metabolomics have been described before [ 35 , 36 ]. Thus, we decided to analyze separately males and females.…”

Section: Resultsmentioning

confidence: 99%

Biochemical Properties of Atranorin-Induced Behavioral and Systematic Changes of Laboratory Rats

Simko

Leškaničová

Suváková

et al. 2022

Life

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Atranorin (ATR) is a secondary metabolite of lichens. While previous studies investigated the effects of this substance predominantly in an in vitro environment, in our study we investigated the basic physicochemical properties, the binding affinity to human serum albumin (HSA), basic pharmacokinetics, and, mainly, on the systematic effects of ATR in vivo. Sporadic studies describe its effects during, predominantly, cancer. This project is original in terms of testing the efficacy of ATR on a healthy organism, where we can possibly attribute negative effects directly to ATR and not to the disease. For the experiment, 24 Sprague Dawley rats (Velaz, Únetice, Czech Republic) were used. The animals were divided into four groups. The first group (n = 6) included healthy males as control intact rats (♂INT) and the second group (n = 6) included healthy females as control intact rats (♀INT). Groups three and four (♂ATR/n = 6 and ♀ATR/n = 6) consisted of animals with daily administered ATR (10mg/kg body weight) in an ethanol–water solution per os for a one-month period. Our results demonstrate that ATR binds to HSA near the binding site TRP214 and acts on a systemic level. ATR caused mild anemia during the treatment. However, based on the levels of hepatic enzymes in the blood (ALT, ALP, or bilirubin levels), thiobarbituric acid reactive substances (TBARS), or liver histology, no impact on liver was recorded. Significantly increased creatinine and lactate dehydrogenase levels together with increased defecation activity during behavioral testing may indicate the anabolic effect of ATR in skeletal muscles. Interestingly, ATR changed some forms of behavior. ATR at a dose of 10 mg/kg body weight is non-toxic and, therefore, could be used in further research.

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“…We acknowledge that these pathways may contribute unequally and vary depending on several factors such as age, gender, body mass index, dietary regimen, stage of the disease and others. For example, the liver is a sexual dimorphic organ, and at least in healthy rats, significant sex-related changes in urea cycle were found ( 66 ). Therefore, studies addressing the discovery of organ-specific biomarkers panels to be used as surrogates of the main metabolic pathways underlying deregulated nitrogen metabolism in Fatty Liver Disease are relevant.…”

Section: Discussionmentioning

confidence: 99%

Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease

2022

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The homeostasis of the most important nitrogen-containing intermediates, ammonia and glutamine, is a tightly regulated process in which the gut-liver axis plays a central role. Several studies revealed that nitrogen metabolism is altered in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), a consensus-driven novel nomenclature for Non-Alcoholic Fatty Liver Disease (NAFLD), the most common chronic liver disease worldwide. Both increased ammonia production by gut microbiota and decreased ammonia hepatic removal due to impaired hepatic urea cycle activity or disrupted glutamine synthetase activity may contribute to hepatic ammonia accumulation underlying steatosis, which can eventually progress to hyperammonemia in more advanced stages of steatohepatitis and overt liver fibrosis. Furthermore, our group recently showed that augmented hepatic ammoniagenesis via increased glutaminase activity and overexpression of the high activity glutaminase 1 isoenzyme occurs in Fatty Liver Disease. Overall, the improved knowledge of disrupted nitrogen metabolism and metabolic miscommunication between the gut and the liver suggests that the reestablishment of altered gut-liver axis nitrogenous balance is an appealing and attractive therapeutic approach to tackle Fatty Liver Disease, a growing and unmet health problem.

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Sexual Dimorphism in Energy Metabolism of Wistar Rats Using Data Analysis

Cited by 18 publications

References 35 publications

Strain-Specific Liver Metabolite Profiles in Medaka

Strain-Specific Liver Metabolite Profiles in Medaka

Biochemical Properties of Atranorin-Induced Behavioral and Systematic Changes of Laboratory Rats

Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease

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