Nutrient-related metabolite profiles explain differences in body composition and size in Nile tilapia (Oreochromis niloticus) from different lakes

This study investigated how metabolite analysis can explain differences in tissue composition and size in fish from different habitats. We, therefore, studied Nile tilapia (Oreochromis niloticus) from three Ethiopian lakes (Gilgel Gibe, Ziway, and Langano) using dried bloodspot (DBS) analysis of carnitine esters and free amino acids. A total of sixty (N = 60) Nile tilapia samples were collected comprising twenty (n = 20) fish from each lake. The proximate composition of the targeted tissues (muscle, skin, gill, gut, and liver) were analyzed. The DBS samples were analyzed for acylcarnitine and free amino acid profiles using quantitative electrospray tandem mass spectrometry. Metabolite ratios were calculated from relevant biochemical pathways that could identify relative changes in nutrient metabolism. The mean weight of Nile tilapia sampled from each lake showed weight variation among the lakes, fish from Lake Ziway were largest (178 g), followed by Gilgel Gibe reservoir (134 g) and Lake Langano (118 g). Fish from Gilgel Gibe showed significantly higher fat composition in all tissues (P < 0.05) except the liver in which no significant variation was observed. The source of fish affected the tissue fat composition. Marked differences were observed in Nile tilapia metabolic activity between the lakes. For instance, the lower body weight and condition of the fish in Lake Langano coincided with several metabolite ratios pointing to a low flow of glucogenic substrate to the citric acid cycle. The low propionyl to acetylcarnitine ratio (C3:C2) in Gilgel Gibe fish is indicating that more of the available acetyl CoA is not led into the citric acid cycle, but instead will be used for fat synthesis. The metabolic markers for lipogenesis and metabolic rate could explain the high-fat concentration in several parts of the body composition of fish from Gilgel Gibe. Our results show that nutrition-related blood metabolite ratios are useful to understand the underlying metabolic events leading to the habitat-dependent differences in the growth of Nile tilapia, and by extension, other species.

Multiomics reveals the genomic, proteomic and metabolic influences of histidyl dipeptides on heart

Histidyl dipeptides, are synthesized in the heart via enzyme carnosine synthase (Carns), which facilitates glycolysis and glucose oxidation by proton buffering and attenuate ischemia and reperfusion injury. However, a composite understanding of the histidyl dipeptide mediated responses in the heart are lacking. We performed multilayer omics in the cardio specific Carns overexpressing mice, showing higher myocardial levels of histidyl dipeptides lead to extensive changes in microRNAs that could target the expression of contractile proteins and enzymes involved in β-fatty acid oxidation and citric acid cycle (TCA). Similarly, global proteomics showed contractile function, fatty acid degradation and TCA cycle, pathways were enriched in the CarnsTg heart. Parallel with these changes, free fatty acids, and TCA intermediate-succinic acid were lower under aerobic and significantly attenuated under anaerobic conditions in the CarnsTg heart. Integration of multiomics data shows β-fatty acid oxidation and TCA cycle exhibit correlative changes at all three levels in CarnsTg heart, suggesting histidyl dipeptides are critical regulators of myocardial structure, function and energetics.

Coenzyme Q10. Structure, role, sources and application in cosmetology

Cell division, the synthesis of amino acids, glycosaminoglycans and enzymes as well as the maturation of collagen and elastin fibers are the basic processes that take place in healthy skin. These reactions are possible due to participation of cellular energy of ATP (adenosine triphosphate), which is produced inside the mitochondria. Within one eukaryotic cell there are from several to several thousand mitochondria. The process of producing energy in the mitochondria is called cellular respiration, known also as the citric acid cycle or the Krebs cycle. Coenzyme Q10 is a key carrier of electrons in the respiratory chain. At the same time, it is responsible for the neutralization of free radicals formed in the Krebs cycle, leading to reduction oxidative stress and minimalization the aging processes of tissues. The article presents the collected information on coenzyme Q10, its structure, role, sources and application in cosmetology. Supplementation in case of coenzyme Q10 deficiency in the skin is possible through the use of appropriate cosmetic preparations, cosmetology treatments and dietary supplements.

Proteomics reveals disturbances in the immune response and energy metabolism of monocytes from patients with septic shock

Sepsis results from a dyshomeostatic response to infection, which may lead to hyper or hypoimmune states. Monocytes are central regulators of the inflammatory response, but our understanding of their role in the genesis and resolution of sepsis is still limited. Here, we report a comprehensive exploration of monocyte molecular responses in a cohort of patients with septic shock via proteomic profiling. The acute stage of septic shock was associated with an impaired inflammatory phenotype, indicated by the down-regulation of MHC class II molecules and proinflammatory cytokine pathways. Simultaneously, there was an up-regulation of glycolysis enzymes and a decrease in proteins related to the citric acid cycle and oxidative phosphorylation. On the other hand, the restoration of immunocompetence was the hallmark of recovering patients, in which an upregulation of interferon signaling pathways was a notable feature. Our results provide insights into the immunopathology of sepsis and propose that, pending future studies, immunometabolism pathway components could serve as therapeutic targets in septic patients.

Effective Detection and Monitoring of Glioma Using [18F]FPIA PET Imaging

Background: Reprogrammed cellular metabolism is a cancer hallmark. In addition to increased glycolysis, the oxidation of acetate in the citric acid cycle is another common metabolic phenotype. We have recently developed a novel fluorine-18-labelled trimethylacetate-based radiotracer, [18F]fluoro-pivalic acid ([18F]FPIA), for imaging the transcellular flux of short-chain fatty acids, and investigated whether this radiotracer can be used for the detection of glioma growth. Methods: We evaluated the potential of [18F]FPIA PET to monitor tumor growth in orthotopic patient-derived (HSJD-GBM-001) and cell line-derived (U87, LN229) glioma xenografts, and also included [18F]FDG PET for comparison. We assessed proliferation (Ki-67) and the expression of lipid metabolism and transport proteins (CPT1, SLC22A2, SLC22A5, SLC25A20) by immunohistochemistry, along with etomoxir treatment to provide insights into [18F]FPIA uptake. Results: Longitudinal PET imaging showed gradual increase in [18F]FPIA uptake in orthotopic glioma models with disease progression (p < 0.0001), and high tumor-to-brain contrast compared to [18F]FDG (p < 0.0001). [18F]FPIA uptake correlated positively with Ki-67 (p < 0.01), SLC22A5 (p < 0.001) and SLC25A20 (p = 0.001), and negatively with CPT1 (p < 0.01) and SLC22A2 (p < 0.01). Etomoxir reduced [18F]FPIA uptake, which correlated with decreased Ki-67 (p < 0.05). Conclusions: Our findings support the use of [18F]FPIA PET for the detection and longitudinal monitoring of glioma, showing a positive correlation with tumor proliferation, and suggest transcellular flux-mediated radiotracer uptake.

Actoprotective Activity of Dimethylaminoethanol Compounds Combined with Intermediates of the Citric Acid Cycle

The article presents the results of evaluation of actoprotective activity of combined dimethylaminoethanol compounds containing intermediates of the citric acid cycle (L-malate, α-ketoglutarate, succinate and fumarate). The effect of long-term intragastric administration of pharmacological agents for 4 weeks at a dose of 75 mg/kg on the static, dynamic endurance, motor coordination and body weight gain of “trained” laboratory animals was assessed in comparison with reference actoprotector ethylthiobenzimidazole (25 mg/kg, intragastrically). It was found that the most promising substances for further study are alpha-ketoglutarate and succinate compounds. After 1 month of training, dynamic endurance and coordination of movements were most infl uenced by DMAE-malate (increase by 60%, p=0.011), static endurance was increased during the 2nd week by DMAE-malate (by 16%, p=0.005) and DMAE-ketoglutarate (by 15.8%, p=0.006), on the 4th week – DMAE-ketoglutarate (by 19.7%, p=0.0001) and DMAE-succinate (by 12.2%, p=0.003). A pronounced body weight increase was observed in the group receiving DMAE-ketoglutarate (by 29%, p=0.022). In general, combined compounds of dimethylaminoethanol with alpha-ketoglutarate, malate and succinate showed the highest actoprotective activity.

Effect of the electric field at 50 Hz and variable intensities on biochemical markers in the honey bee’s hemolymph

The amount of artificial electromagnetic fields of various parameters in the honey bee’s environment increases globally. So far, it had been proven that exposure to an E-field at 50 Hz can cause changes in bee’s behavior, alter the activity of proteases, and enzymatic antioxidants. Due to the potentially harmful effect of this factor on honey bees, we decided to investigate the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), and the concentration of albumin and creatinine in bee’s hemolymph after exposure to 50 Hz E-field. Honey bee workers were placed in wooden cages (200 × 150 × 70 mm) and exposed to the 50 Hz E-field with the intensity of <1, 5.0, 11.5, 23.0, or 34.5 kV/m for 1, 3, 6, or 12h. A homogeneous 50 Hz E-field was generated in the form of a plate capacitor. Hemolymph samples for analysis were taken immediately after the end of exposure to the E-field from 100 bees from each group. According to our study, the activity of AST, ALT, and ALP in honey bees’ hemolymph decreased after exposure to 50 Hz E-field with various intensities. The decrease in AST, ALT, and ALP activity intensified with prolonged exposure time. 50 Hz E-field may cause the impairment of crucial metabolic cycles in the honey bees’ organism (such as the citric acid cycle, ATP synthesis, oxidative phosphorylation, β-oxidation). Moreover, exposure to E-Field altered the concentration of creatinine and albumin, which are important non-enzymatic antioxidants. Such changes may indicate a disturbance in protein metabolism and increased muscle activity.

A photo-switchable yeast isocitrate dehydrogenase to control metabolic flux through the citric acid cycle

For various research questions in metabolism, it is highly desirable to have means available, with which the flux through specific pathways can be perturbed dynamically, in a reversible manner, and at a timescale that is consistent with the fast turnover rates of metabolism. Optogenetics, in principle, offers such possibility. Here, we developed an initial version of a photo-switchable isocitrate dehydrogenase (IDH) aimed at controlling the metabolic flux through the citric acid cycle in budding yeast. By inserting a protein-based light switch (LOV2) into computationally identified active/regulatory-coupled sites of IDH and by using in vivo screening in Saccharomyces cerevisiae, we obtained a number of IDH enzymes whose activity can be switched by light. Subsequent in-vivo characterization and optimization resulted in an initial version of photo-switchable (PS) IDH. While further improvements of the enzyme are necessary, our study demonstrates the efficacy of the overall approach from computational design, via in vivo screening and characterization. It also represents one of the first few examples, where optogenetics were used to control the activity of a metabolic enzyme.

Emodin and rhein in Cassia tora ameliorates activity of mitochondrial enzymes involved in oxidative phosphorylation in the retina of diabetic mice

Cassia tora is an annual herb, which has pharmacological effects such as antioxidant, hypolipidemic, and antidiabetic effects. Accordingly, its effect on diabetes has been well-studied. However, it is unclear whether it has an effect on mitochondrial dysfunction associated with diabetes. In this study, the effects of emodin and rhein in C. tora seed ethanolic extract (ER/CSEE) on retinal mitochondrial function were examined in high-fat diet (HFD)-fed mice. HFD-fed mice exhibited decreased mitochondrial function followed by compensatory increase in the expression levels of mitochondrial enzymes. However, ER/CSEE treatment for 12 weeks ameliorated the activity of retinal mitochondrial complexes and reduced the expression level of enzymes involved in oxidative phosphorylation, except that of complex II and citrate synthase in citric acid cycle. This suggests that repairing capacity of enzymes in electron transport chain and citric acid cycle of mitochondria are different in response to the metabolic state. Therefore, it concluded that emodin and rhein play a pharmacological role in fat metabolism by influencing activities of enzymes in citric acid cycle linked with beta-oxidation in retina.