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Phospholipid metabolism, including phosphatidylcholine (PC) biosynthesis, is crucial for various biological functions and is associated with longevity. Phosphatidylethanolamine N-methyltransferase (PEMT) is a protein that catalyzes the biosynthesis of PC, the levels of which change in various organs such as the brain and kidneys during aging. However, the role of PEMT for systemic PC supply is not fully understood. To address how PEMT affects aging-associated energy metabolism in tissues responsible for nutrient absorption, lipid storage, and energy consumption, we employed NMR-based metabolomics to study the liver, plasma, intestine (duodenum, jejunum, and ileum), brown/white adipose tissues (BAT and WAT), and skeletal muscle of young (9–10 weeks) and old (91–132 weeks) wild-type (WT) and PEMT knockout (KO) mice. We found that the effect of PEMT-knockout was tissue-specific and age-dependent. A deficiency of PEMT affected the metabolome of all tissues examined, among which the metabolome of BAT from both young and aged KO mice was dramatically changed in comparison to the WT mice, whereas the metabolome of the jejunum was only slightly affected. As for aging, the absence of PEMT increased the divergence of the metabolome during the aging of the liver, WAT, duodenum, and ileum and decreased the impact on skeletal muscle. Overall, our results suggest that PEMT plays a previously underexplored, critical role in both aging and energy metabolism. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is a worldwide health burden. Metabolomics analysis has revealed HBV-induced metabolism dysregulation in liver tissues and hepatocytes. However, as an infectious disease, the tissue-specific landscape of metabolic profiles of HBV infection remains unclear. To fill this gap, we applied untargeted nuclear magnetic resonance (NMR) metabolomic analysis of the heart, liver, spleen, lung, kidney, pancreas, and intestine (duodenum, jejunum, ileum) in HBV-transgenic mice and their wild-type littermates. Strikingly, we found systemic metabolic alterations induced by HBV in liver and extrahepatic organs. Significant changes in metabolites have been observed in most tissues of HBV-transgenic mice, except for ileum. The metabolic changes may provide novel therapeutic targets for the treatment of HBV infection. Moreover, tissue-specific metabolic profiles could speed up the study of HBV induced systemic metabolic reprogramming, which could help follow the progression of HBV infection and explain the underlying pathogenesis. [ABSTRACT FROM AUTHOR]

Excessive exposure to light is a global issue. Artificial light pollution has been shown to disrupt the body's natural circadian rhythm. To investigate the impacts of light on metabolism, we studied Sprague-Dawley rats chronically exposed to red or blue light during daytime or nighttime. Rats in the experimental group were exposed to extended light for 4 hours during daytime or nighttime to simulate the effects of excessive light usage. Strikingly, we found systemic metabolic alterations only induced by blue light during daytime. Furthermore, we conducted metabolomic analyses of the cerebrospinal fluid, serum, heart, liver, spleen, adrenal, cerebellum, pituitary, prostate, spermatophore, hypothalamus and kidney from rats in the control and blue light exposure during daytime. Significant changes in metabolites have been observed in cerebrospinal fluid, serum, hypothalamus and kidney of rats exposed to blue light during daytime. Metabolic alterations observed in rats encompassing pyruvate metabolism, glutathione metabolism homocysteine degradation, phosphatidylethanolamine biosynthesis, and phospholipid biosynthesis, exhibit analogous patterns to those inherent in specific physiological processes, notably neurodevelopment, cellular injury, oxidative stress, and autophagic pathways. Our study provides insights into tissue-specific metabolic changes in rats exposed to blue light during the daytime and may help explain potential mechanisms of photopathogenesis. [Display omitted] • We conducted a metabolomic analysis of light-exposure in rats by NMR spectroscopy. • Blue light exposure during daytime induced metabolic alterations in rats. • Metabolic changes occur in cerebrospinal fluid, serum, hypothalamus and kidney. • Alterations provide insights into potential mechanisms of photopathogenesis. [ABSTRACT FROM AUTHOR]

Energy metabolism, including alterations in energy intake and expenditure, is closely related to aging and longevity. Metabolomics studies have recently unraveled changes in metabolite composition in plasma and tissues during aging and have provided critical information to elucidate the molecular basis of the aging process. However, the metabolic changes in tissues responsible for food intake and lipid storage have remained unexplored. In this study, we aimed to investigate aging-related metabolic alterations in these tissues. To fill this gap, we employed NMR-based metabolomics in several tissues, including different parts of the intestine (duodenum, jejunum, ileum) and brown/white adipose tissues (BAT, WAT), of young (9–10 weeks) and old (96–104 weeks) wild-type (mixed genetic background of 129/J and C57BL/6) mice. We, further, included plasma and skeletal muscle of the same mice to verify previous results. Strikingly, we found that duodenum, jejunum, ileum, and WAT do not metabolically age. In contrast, plasma, skeletal muscle, and BAT show a strong metabolic aging phenotype. Overall, we provide first insights into the metabolic changes of tissues essential for nutrient uptake and lipid storage and have identified biomarkers for metabolites that could be further explored, to study the molecular mechanisms of aging. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolic reprogramming is a hallmark of malignancy. Hepatocellular carcinoma (HCC) cancer cells alterations in metabolism are due to the adaption to hypoxia and hypo-nutrient conditions. Several proteins and metabolites associated with glycolysis, tricarboxylic acid cycle and pyrimidine synthesis were found to be differentially regulated in serum, tumor and peritumoral tissues with increased tumor size, suggesting that microenvironment and tumor cell cooperate to regulate metabolism. In this study, the metabolomic characterization of HCC using paired tumor and adjacent liver tissues indicated tumor size-dependent metabolic reprogramming. Targeting cancer metabolism provides potential diagnostic and prognostic metabolic biomarkers. Our study brings new insight into the potential therapeutic use of metabolic targets and a methodological framework and diagnostic and prognostic metabolic markers that may be used in a clinical setting. The stratification of future clinical trials based on these metabolic subsets should improve the development of effective therapies and more intensive surveillance. Hepatocellular carcinoma (HCC) is a common malignancy with poor prognosis, high morbidity and mortality concerning with lack of effective diagnosis and high postoperative recurrence. Similar with other cancers, HCC cancer cells have to alter their metabolism to adapt to the changing requirements imposed by the environment of the growing tumor. In less vascularized regions of tumor, cancer cells experience hypoxia and nutrient starvation. Here, we show that HCC undergoes a global metabolic reprogramming during tumor growth. A combined proteomics and metabolomics analysis of paired peritumoral and tumor tissues from 200 HCC patients revealed liver-specific metabolic reprogramming and metabolic alterations with increasing tumor sizes. Several proteins and metabolites associated with glycolysis, the tricarboxylic acid cycle and pyrimidine synthesis were found to be differentially regulated in serum, tumor and peritumoral tissue with increased tumor sizes. Several prognostic metabolite biomarkers involved in HCC metabolic reprogramming were identified and integrated with clinical and pathological data. We built and validated this combined model to discriminate against patients with different recurrence risks. An integrated and comprehensive metabolomic analysis of HCC is provided by our present work. Metabolomic alterations associated with the advanced stage of the disease and poor clinical outcomes, were revealed. Targeting cancer metabolism may deliver effective therapies for HCC. [ABSTRACT FROM AUTHOR]

The dysregulation of cellular metabolism is a hallmark of ageing. To understand the metabolic changes that occur as a consequence of the ageing process and to find biomarkers for age-related diseases, we conducted metabolomic analyses of the brain, heart, kidney, liver, lung and spleen in young (9–10 weeks) and old (96–104 weeks) wild-type mice [mixed genetic background of 129/J and C57BL/6] using NMR spectroscopy. We found differences in the metabolic fingerprints of all tissues and distinguished several metabolites to be altered in most tissues, suggesting that they may be universal biomarkers of ageing. In addition, we found distinct tissue-clustered sets of metabolites throughout the organism. The associated metabolic changes may reveal novel therapeutic targets for the treatment of ageing and age-related diseases. Moreover, the identified metabolite biomarkers could provide a sensitive molecular read-out to determine the age of biologic tissues and organs and to validate the effectiveness and potential off-target effects of senolytic drug candidates on both a systemic and tissue-specific level. [ABSTRACT FROM AUTHOR]