The Brain Metabolome of Male Rats across the Lifespan

Zheng, Xiaojiao; Chen, Tianlu; Zhao, Aihua; Wang, Xiaoyan; Xie, Guoxiang; Huang, Fengjie; Liu, Jiajian; Zhao, Qing; Wang, Shouli; Wang, Chongchong; Zhou, Mingmei; Panee, Jun; He, Zhigang; Wang, Jia

doi:10.1038/srep24125

Cited by 61 publications

(60 citation statements)

References 56 publications

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“…The impact of age on the CNS metabolome is nowadays an object of study, with one the most recent aiming to describe the brain metabolome of rats throughout their lifespan. The analyses proved that compared with regional differences, age contributed more substantially to the detected differences [ 38 ]. Differences in metabolites concentrations may be due to a number of factors related to both cerebral and systemic processes, including the maturation of the Blood-Brain-Barrier (BBB), age-related differences in brain metabolic rates and blood composition.…”

Section: Discussionmentioning

confidence: 99%

Age-Related 1H NMR Characterization of Cerebrospinal Fluid in Newborn and Young Healthy Piglets

et al. 2016

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When it comes to neuroscience, pigs represent an important animal model due to their resemblance with humans’ brains for several patterns including anatomy and developmental stages. Cerebrospinal fluid (CSF) is a relatively easy-to-collect specimen that can provide important information about neurological health and function, proving its importance as both a diagnostic and biomedical monitoring tool. Consequently, it would be of high scientific interest and value to obtain more standard physiological information regarding its composition and dynamics for both swine pathology and the refinement of experimental protocols. Recently, proton nuclear magnetic resonance (1H NMR) spectroscopy has been applied in order to analyze the metabolomic profile of this biological fluid, and results showed the technique to be highly reproducible and reliable. The aim of the present study was to investigate in both qualitative and quantitative manner the composition of Cerebrospinal Fluid harvested form healthy newborn (5 days old-P5) and young (30-P30 and 50-P50 days old) piglets using 1H NMR Spectroscopy, and to analyze any possible difference in metabolites concentration between age groups, related to age and Blood-Brain-Barrier maturation. On each of the analyzed samples, 30 molecules could be observed above their limit of quantification, accounting for 95–98% of the total area of the spectra. The concentrations of adenine, tyrosine, leucine, valine, 3-hydroxyvalerate, 3-methyl-2-oxovalerate were found to decrease between P05 and P50, while the concentrations of glutamine, creatinine, methanol, trimethylamine and myo-inositol were found to increase. The P05-P30 comparison was also significant for glutamine, creatinine, adenine, tyrosine, leucine, valine, 3-hydroxyisovalerate, 3-methyl-2-oxovalerate, while for the P30-P50 comparison we found significant differences for glutamine, myo-inositol, leucine and trimethylamine. None of these molecules showed at P30 concentrations outside the P05 –P50 range.

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Section: Discussionmentioning

confidence: 99%

Age-Related 1H NMR Characterization of Cerebrospinal Fluid in Newborn and Young Healthy Piglets

et al. 2016

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“…Identifying the biochemical alterations related to different diets provide valuable insights into the associations between metabolism and phenotypes [22][23][24][25][26]. Global metabolomics captures system end point responses to these biological perturbations by measuring the chemical compositions of biological samples, such as biofluids and tissues.…”

Section: Introductionmentioning

confidence: 99%

Calorie restriction and its impact on gut microbial composition and global metabolism

Zheng

Wang

2018

Front. Med.

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Calorie restriction (CR) is a dietary regimen that reduces calorie intake without incurring malnutrition or a reduction in essential nutrients. It has long been recognized as a natural strategy for promoting health, extending longevity, and prevents the development of metabolic and age-related diseases. In the present review, we focus on the general effect of CR on gut microbiota composition and global metabolism. We also propose mechanisms for its beneficial effect. Results showed that probiotic and butyrate-producing microbes increased their relative abundance, whereas proinflammatory strains exhibited suppressed relative abundance following CR. Analyses of the gut microbial and host metabolisms revealed that most host microbial co-metabolites were changed due to CR. Examples of dramatic CR-induced changes in host metabolism included a decrease in the rate of lipid biosynthesis and an increase in the rates of fatty acid catabolism, β-oxidation, glycogenolysis, and gluconeogenesis. The observed phenotypes and the further verification of the direct link between gut microbiota and metabolome may benefit patients that are at risk for developing metabolic disease. Thus, improved gut microbiota composition and metabolome are potential biomarkers for determining the effectiveness of dietary interventions for age-related and metabolic diseases.

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“…Interestingly, BAs and these two receptors are also present in the central nervous system (Mano et al 2004a, McMillin et al 2016, Zheng et al 2016). More specifically, TGR5 protein was detected in neurons and glia cells in rat and human brains using immunohistochemistry (Keitel et al 2010) and FXR was present and active in mouse brain .…”

Section: Introductionmentioning

confidence: 99%

Chronic infusion of taurolithocholate into the brain increases fat oxidation in mice

Eggink

Tambyrajah

Berg

et al. 2018

Journal of Endocrinology

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Bile acids can function in the postprandial state as circulating signaling molecules in the regulation of glucose and lipid metabolism via the transmembrane receptor TGR5 and nuclear receptor FXR. Both receptors are present in the central nervous system, but their function in the brain is unclear. Therefore, we investigated the effects of intracerebroventricular (i.c.v.) administration of taurolithocholate (tLCA), a strong TGR5 agonist, and GW4064, a synthetic FXR agonist, on energy metabolism. We determined the effects of chronic i.c.v. infusion of tLCA, GW4064, or vehicle on energy expenditure, body weight and composition as well as tissue specific fatty acid uptake in mice equipped with osmotic minipumps. We found that i.c.v. administration of tLCA (final concentration in cerebrospinal fluid: 1 μM) increased fat oxidation (tLCA group: 0.083 ± 0.006 vs control group: 0.036 ± 0.023 kcal/h, = 5.46, = 0.04) and decreased fat mass (after 9 days of tLCA infusion: 1.35 ± 0.13 vs controls: 1.96 ± 0.23 g, = 0.03). These changes were associated with enhanced uptake of triglyceride-derived fatty acids by brown adipose tissue and with browning of subcutaneous white adipose tissue. I.c.v. administration of GW4064 (final concentration in cerebrospinal fluid: 10 μM) did not affect energy metabolism, body composition nor bile acid levels, negating a role of FXR in the central nervous system in metabolic control. In conclusion, bile acids such as tLCA may exert metabolic effects on fat metabolism via the brain.

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The Brain Metabolome of Male Rats across the Lifespan

Cited by 61 publications

References 56 publications

Age-Related 1H NMR Characterization of Cerebrospinal Fluid in Newborn and Young Healthy Piglets

Age-Related 1H NMR Characterization of Cerebrospinal Fluid in Newborn and Young Healthy Piglets

Calorie restriction and its impact on gut microbial composition and global metabolism

Chronic infusion of taurolithocholate into the brain increases fat oxidation in mice

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