Nejvíce citovaný článek - PubMed ID 37584663
LORA, Lipid Over-Representation Analysis Based on Structural Information
The ontogenesis of the circadian clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and its sensitivity to maternal signals are not fully understood. Here, we investigated the development of the clock in the rat SCN from the fetal to the postweaning period and identified rhythmic metabolic signals from the mother to the fetal SCN. We determined daily expression profiles of clock genes (Per2, Nr1d1, Bmal1) and clock- and metabolism-related genes (Dbp, E4bp4) and performed time-resolved analysis of the metabolome and lipidome in the SCN and plasma of 19-day-old embryos (E19) and 2-, 10-, 20-, and 28-day-old pups (P02-28). Our data show that rhythms in the expression of canonical clock genes are absent at E19 and develop gradually until P10, but the Dbp rhythm was still developing between P20 and P28. Expression of the metabolism-sensitive gene E4bp4 and levels of essential amino acids and other metabolites supplied by maternal food are rhythmic in the fetal SCN, which is lost after birth at P02 and reappears later in the postnatal period. Maternal food-derived metabolites were also rhythmic in fetal plasma. The temporal coherence of the fetal SCN metabolome and lipidome declines markedly and its rhythmicity disappears immediately after birth. The results revealed previously unforeseen pathways by which the fetal SCN may receive rhythmic information from the mother before its clock develops.
- MeSH
- cirkadiánní hodiny * fyziologie genetika MeSH
- cirkadiánní proteiny Period genetika metabolismus MeSH
- cirkadiánní rytmus fyziologie MeSH
- krysa rodu Rattus MeSH
- metabolom MeSH
- nucleus suprachiasmaticus * metabolismus embryologie fyziologie MeSH
- proteiny CLOCK genetika metabolismus MeSH
- těhotenství MeSH
- transkripční faktory ARNTL genetika metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cirkadiánní proteiny Period MeSH
- proteiny CLOCK MeSH
- transkripční faktory ARNTL MeSH
Circadian rhythms regulate key physiological processes through clock genes in central and peripheral tissues. While circadian gene expression during development has been well studied, the temporal dynamics of metabolism across tissues remain less understood. Here, we present the Circadian Ontogenetic Metabolomics Atlas (COMA), which maps circadian metabolic rhythms across 16 rat anatomical structures. The brain (suprachiasmatic nuclei, medial prefrontal cortex) and periphery (liver, plasma) span developmental stages from embryonic E19 to postnatal P2, P10, P20, and P28. Fecal samples include all four postnatal stages, while additional peripheral tissues were analyzed at P20 and P28. Using a multiplatform liquid chromatography-mass spectrometry approach, we annotated 851 metabolites from 1610 samples. We identified distinct circadian shifts, particularly during the transition from nursing to solid food intake (P10-P20), with an average of 24% of metabolites exhibiting circadian oscillations across sample types, as determined by JTK_CYCLE. Our study also underscores the importance of standardized sampling, as metabolite intensities fluctuate with both circadian rhythms and development. COMA serves as an open-access resource ( https://coma.metabolomics.fgu.cas.cz ) for exploring circadian metabolic regulation and its role in developmental biology.
- Klíčová slova
- Atlas, Circadian rhythm, Lipidomics, Metabolomics, Resource,
- MeSH
- chromatografie kapalinová MeSH
- cirkadiánní rytmus * fyziologie MeSH
- feces * chemie MeSH
- játra metabolismus MeSH
- krysa rodu Rattus MeSH
- metabolom * MeSH
- metabolomika * metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Metabolomics and lipidomics have emerged as tools in understanding the connections of metabolic syndrome (MetS) with cardiovascular diseases (CVD), type 1 and type 2 diabetes (T1D, T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). This review highlights the applications of these omics approaches in large-scale cohort studies, emphasizing their role in biomarker discovery and disease prediction. Integrating metabolomics and lipidomics has significantly advanced our understanding of MetS pathology by identifying unique metabolic signatures associated with disease progression. However, challenges such as standardizing analytical workflows, data interpretation, and biomarker validation remain critical for translating research findings into clinical practice. Future research should focus on optimizing these methodologies to enhance their clinical utility and address the global burden of MetS-related diseases.
- MeSH
- biologické markery metabolismus MeSH
- diabetes mellitus 1. typu metabolismus komplikace MeSH
- diabetes mellitus 2. typu * metabolismus MeSH
- kardiovaskulární nemoci * metabolismus diagnóza MeSH
- lidé MeSH
- lipidomika * metody MeSH
- metabolický syndrom * metabolismus MeSH
- metabolomika * metody MeSH
- ztučnělá játra metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
Acylcarnitines are important markers in metabolic studies of many diseases, including metabolic, cardiovascular, and neurological disorders. We reviewed analytical methods for analyzing acylcarnitines with respect to the available molecular structural information, the technical limitations of legacy methods, and the potential of new mass spectrometry-based techniques to provide new information on metabolite structure. We summarized the nomenclature of acylcarnitines based on historical common names and common abbreviations, and we propose the use of systematic abbreviations derived from the shorthand notation for lipid structures. The transition to systematic nomenclature will facilitate acylcarnitine annotation, reporting, and standardization in metabolomics. We have reviewed the metabolic origins of acylcarnitines important for the biological interpretation of human metabolomic profiles. We identified neglected isomers of acylcarnitines and summarized the metabolic pathways involved in the synthesis and degradation of acylcarnitines, including branched-chain lipids and amino acids. We reviewed the primary literature, mapped the metabolic transformations of acyl-CoAs to acylcarnitines, and created a freely available WikiPathway WP5423 to help researchers navigate the acylcarnitine field. The WikiPathway was curated, metabolites and metabolic reactions were annotated, and references were included. We also provide a table for conversion between common names and abbreviations and systematic abbreviations linked to the LIPID MAPS or Human Metabolome Database.
- MeSH
- karnitin * analogy a deriváty metabolismus biosyntéza MeSH
- lidé MeSH
- metabolické sítě a dráhy * MeSH
- metabolomika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- acylcarnitine MeSH Prohlížeč
- karnitin * MeSH
Fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase. Additionally, tissue-specific differences in FAHFA levels, focusing on the perigonadal white adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), brown adipose tissue (BAT), plasma, and liver, were evaluated using metabolomics and lipidomics. We found that female mice exhibited higher FAHFA levels in pgWAT, scWAT, and BAT compared to males. FAHFA levels were inversely related to Adtrp mRNA, which showed significantly lower expression in females compared with males in pgWAT and scWAT. However, no significant differences between the sexes were observed in plasma and liver FAHFA levels. Adtrp deletion had minimal impact on both sexes' metabolome and lipidome of pgWAT. However, we discovered higher endogenous levels of triacylglycerol estolides containing FAHFAs, a FAHFA metabolic reservoir, in the pgWAT of female mice. These findings suggest that sex-dependent differences in FAHFA levels occur primarily in specific WAT depots and may modulate local insulin sensitivity in adipocytes. However, further investigations are warranted to fully comprehend the underlying mechanisms and implications of sex effects on FAHFA metabolism in humans.
- Klíčová slova
- Adtrp, FAHFA, adipose tissue, female, lipokines, male,
- Publikační typ
- časopisecké články MeSH
- preprinty MeSH