FROM A NON‐TARGETED METABOLOMICS APPROACH TO A TARGETED BIOMARKERS STRATEGY TO HIGHLIGHT TESTOSTERONE ABUSE IN EQUINE. ILLUSTRATION OF A METHODOLOGICAL TRANSFER BETWEEN PLATFORMS AND LABORATORIES.

Background:: In Traditional Chinese Medicine (TCM), the heads and tails of Angelica sinensis (Oliv.) Diels (AS) is used in treating different diseases due to their different pharmaceutical efficacies. The underline mechanisms, however, have not been fully explored. Objective:: Novel mechanisms responsible for the discrepant activities between AS heads and tails were explored by a combined strategy of transcriptomes and metabolomics. Method:: Six pairs of the heads and tails of AS roots were collected in Min County, China. Total RNA and metabolites, which were used for RNA-seq and untargeted metabolomics analysis, were respectively isolated from each AS sample (0.1 g) by Trizol and methanol reagent. Subsequently, differentially expressed genes (DEGs) and discrepant pharmaceutical metabolites were identified for comparing AS heads and tails. Key DEGs and metabolites were quantified by qRT-PCR and targeted metabolomics experiment. Results:: Comprehensive analysis of transcriptomes and metabolomics results suggested that five KEGG pathways with significant differences included 57 DEGs. Especially, fourteen DEGs and six key metabolites were relation to the metabolic regulation of Phenylpropanoid biosynthesis (PB) pathway. Results of qRT-PCR and targeted metabolomics indicated that higher levels of expression of crucial genes in PB pathway, such as PAL, CAD, COMT and peroxidase in the tail of AS were positively correlated with levels of ferulic acid-related metabolites. The average content of ferulic acid in tails (569.58162.39 nmol/g) was higher than those in the heads (168.73  67.30 nmol/g) (P˂0.01); Caffeic acid in tails (3.82  0.88 nmol/g) vs heads (1.37  0.41 nmol/g) (P˂0.01), and Cinnamic acid in tails (0.24  0.09 nmol/g) vs heads (0.14  0.02 nmol/g) (P˂0.05). Conclusion:: Our work demonstrated that overexpressed genes and accumulated metabolites derived from PB pathway might be responsible for the discrepant pharmaceutical efficacies between AS heads and tails.

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An In Vivo Rat α-D-glucose Stable Isotope Homeostasis Drug Discovery Screen: A Targeted Metabolomics Approach

Current Topics in Medicinal Chemistry ◽

10.2174/1568026617666170707130401 ◽

2017 ◽

Vol 17 (24) ◽

Author(s):

Gary W. Caldwell ◽

Wensheng Lang

Keyword(s):

Drug Discovery ◽

Stable Isotope ◽

Targeted Metabolomics

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P2.11-10 Discovery of Potential Biomarkers That Discriminate Early Stage NSCLC from Controls by Non-Targeted Metabolomics Profiling

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.1710 ◽

2019 ◽

Vol 14 (10) ◽

pp. S795-S796

Author(s):

J. Kim ◽

R. Balshaw ◽

C. Trevena ◽

S. Banerji ◽

L. Murphy ◽

...

Keyword(s):

Early Stage ◽

Targeted Metabolomics ◽

Early Stage Nsclc ◽

Potential Biomarkers

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Muscle metabolome and adipose tissue mRNA expression of lipid metabolism-related genes in over-conditioned dairy cows differing in serum-metabotype

Scientific Reports ◽

10.1038/s41598-021-90577-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hassan Sadri ◽

Morteza Hosseini Ghaffari ◽

Katharina Schuh ◽

Christian Koch ◽

Helga Sauerwein

Keyword(s):

Adipose Tissue ◽

Dairy Cows ◽

Body Condition Score ◽

Subcutaneous Fat ◽

Oxidative Capacity ◽

Mrna Abundance ◽

Targeted Metabolomics ◽

Healthy Humans ◽

Condition Score ◽

Metabolically Healthy

AbstractOver-conditioned dairy cows, classified by body condition score (BCS) and backfat thickness (BFT) are less able to metabolically adapt to the rapidly increasing milk yield after parturition. Based on serum metabolome and cluster analyses, high BCS cows (HBCS) could be classified into metabotypes that are more similar to normal (NBCS) cows, i.e., HBCS predicted normal (HBCS-PN) than the HBCS predicted high (HBCS-PH) cows—similar to the concept of obese but metabolically healthy humans. Our objective was to compare muscle metabolome and mRNA abundance of genes related to lipogenesis and lipolysis in adipose tissue between HBCS-PH (n = 13), HBCS-PN (n = 6), and NBCS-PN (n = 15). Tail-head subcutaneous fat was biopsied on d −49, 3, 21, and 84 relative to parturition. Potential differences in the oxidative capacity of skeletal muscle were assessed by targeted metabolomics in M. semitendinosus from d 21. Besides characteristic changes with time, differences in the mRNA abundance were limited to lipogenesis-related genes on d −49 (HBCS-PH > HBCS-PN). The HBCS-PH had more than two-fold higher muscle concentrations of short (C2, C4-OH, C6-OH) and long-chain acylcarnitines (C16, C18, and C18:1) than HBCS-PN, indicating a greater oxidative capacity for fatty acids (and utilization of ketones) in muscle of HBCS-PN than HBCS-PH cows.

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Metabolomics of aging in primary fibroblasts from small and large breed dogs

GeroScience ◽

10.1007/s11357-021-00388-0 ◽

2021 ◽

Author(s):

Paul S. Brookes ◽

Ana Gabriela Jimenez

Keyword(s):

Aging Process ◽

Tca Cycle ◽

Therapeutic Strategies ◽

Targeted Metabolomics ◽

The Tca Cycle ◽

Age Dependent ◽

Primary Fibroblasts ◽

Aging Rates ◽

Underlying Mechanisms ◽

Coenzyme A Biosynthesis

AbstractAmong several animal groups (eutherian mammals, birds, reptiles), lifespan positively correlates with body mass over several orders of magnitude. Contradicting this pattern are domesticated dogs, with small dog breeds exhibiting significantly longer lifespans than large dog breeds. The underlying mechanisms of differing aging rates across body masses are unclear, but it is generally agreed that metabolism is a significant regulator of the aging process. Herein, we performed a targeted metabolomics analysis on primary fibroblasts isolated from small and large breed young and old dogs. Regardless of size, older dogs exhibited lower glutathione and ATP, consistent with a role for oxidative stress and bioenergetic decline in aging. Furthermore, several size-specific metabolic patterns were observed with aging, including the following: (i) An apparent defect in the lower half of glycolysis in large old dogs at the level of pyruvate kinase. (ii) Increased glutamine anaplerosis into the TCA cycle in large old dogs. (iii) A potential defect in coenzyme A biosynthesis in large old dogs. (iv) Low nucleotide levels in small young dogs that corrected with age. (v) An age-dependent increase in carnitine in small dogs that was absent in large dogs. Overall, these data support the hypothesis that alterations in metabolism may underlie the different lifespans of small vs. large breed dogs, and further work in this area may afford potential therapeutic strategies to improve the lifespan of large dogs.

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