Dexamethasone (Dex) is a synthetic glucocorticoid (GC) drug commonly used clinically for the treatment of several inflammatory and immune-mediated diseases. Despite its broad range of indications, the long-term use of Dex is known to be associated with specific abnormalities in several tissues and organs. In this study, the metabolomic effects on five different organs induced by the chronic administration of Dex in the Sprague–Dawley rat model were investigated using the chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS) platform, which targets the amine/phenol submetabolomes. Compared to controls, a prolonged intake of Dex resulted in significant perturbations in the levels of 492, 442, 300, 186, and 105 metabolites in the brain, skeletal muscle, liver, kidney, and heart tissues, respectively. The positively identified metabolites were mapped to diverse molecular pathways in different organs. In the brain, perturbations in protein biosynthesis, amino acid metabolism, and monoamine neurotransmitter synthesis were identified, while in the heart, pyrimidine metabolism and branched amino acid biosynthesis were the most significantly impaired pathways. In the kidney, several amino acid pathways were dysregulated, which reflected impairments in several biological functions, including gluconeogenesis and ureagenesis. Beta-alanine metabolism and uridine homeostasis were profoundly affected in liver tissues, whereas alterations of glutathione, arginine, glutamine, and nitrogen metabolism pointed to the modulation of muscle metabolism and disturbances in energy production and muscle mass in skeletal muscle. The differential expression of multiple dipeptides was most significant in the liver (down-regulated), brain (up-regulation), and kidney tissues, but not in the heart or skeletal muscle tissues. The identification of clinically relevant pathways provides holistic insights into the tissue molecular responses induced by Dex and understanding of the underlying mechanisms associated with their side effects. Our data suggest a potential role for glutathione supplementation and dipeptide modulators as novel therapeutic interventions to mitigate the side effects induced by Dex therapy.

Vinegar is used as an acidic condiment and preservative worldwide. In Asia, various black vinegars are made from different combinations of grains, such as Sichuan bran vinegar (SBV), Shanxi aged vinegar (SAV), Zhenjiang aromatic vinegar (ZAV), and Fujian Monascus vinegar (FMV) in China and Ehime black vinegar in Japan (JBV). Understanding the chemical compositions of different vinegars can provide information about nutritional values and the quality of the taste. This study investigated the vinegar metabolome using a combination of GC-MS, conventional LC-MS, and chemical isotope labeling LC-MS. Different types of vinegar contained different metabolites and concentrations. Amino acids and organic acids were found to be the main components. Tetrahydroharman-3-carboxylic acid and harmalan were identified first in vinegar. Various diketopiperazines and linear dipeptides contributing to different taste effects were also detected first in vinegar. Dipeptides, 3-phenyllactic acid, and tyrosine were found to be potential metabolic markers for differentiating vinegars. The differently expressed pathway between Chinese and Japanese vinegar was tryptophan metabolism, while the main difference within Chinese vinegars was aminoacyl-tRNA biosynthesis metabolism. These results not only give insights into the metabolites in famous types of cereal vinegar but also provide valuable knowledge for making vinegar with desirable health characteristics.

Background/Objectives: Individuals with metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy are two distinct cardiometabolic populations, each potentially necessitating alternative clinical management. However, our understanding of the unique physiological effects of uncomplicated MHO on fetoplacental growth and metabolism remains limited. In this study, we aimed to identify changes in placental morphology and metabolites associated with maternal obesity, independent of pregnancy-related cardiometabolic complications. Methods: Placentae from women with a prepregnancy body mass index (BMI) < 25 kg/m² (control; n = 15) and women with MHO (prepregnancy BMI > 30 kg/m² with no cardiometabolic diseases; n = 15) were analyzed for indices of placental growth and untargeted metabolomics. Complementary assessments were conducted on proinflammatory genes and antioxidant defense system genes, proteins, and enzymes, along with lipid peroxidation markers. Results: Clear placentomegaly without histopathological changes was observed in uncomplicated MHO pregnancies. The metabolite 3-aminoisobutanoic acid emerged as the top-ranked feature distinguishing placentae from MHO individuals from control placentae, and changes in the cysteine, methionine, and vitamin B6 metabolism pathways were among the most distinct differences identified. Conclusions: These findings illustrate an altered placental morphology and metabolomic profile specific to uncomplicated MHO, offering new insights into how obesity, without cardiometabolic complications, may influence fetoplacental growth and metabolism. They may also represent a crucial first step towards marker identification for MHO pregnancy and underscore the importance of alternative care pathways when obesity is present but metabolic comorbidities are absent.

Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy represent two distinct cardiometabolic populations, each potentially necessitating alternative clin-ical management. However, the understanding of the unique physiological effects of uncomplicated MHO or MUO on fetoplacental growth and metabolism remains limited. This study aimed to identify changes in placental morphology and metabolites concerning maternal obesity, inde-pendent of pregnancy-related cardiometabolic complications. Placentae from women with a pre-pregnancy body mass index (BMI) 30 kg/m² with no cardiometabolic diseases; n = 15) were analysed for indices of placental growth and untargeted metabolomics. Complementary measures of pro-inflammatory and antioxidant genes, as well as antioxidant proteins, enzymes, and lipid peroxidation markers were conducted. A clear placentomegaly without histopathological changes was observed in un-complicated MHO pregnancies. The metabolite 3-aminoisobutanoic acid emerged as the top-ranked feature distinguishing MHO from control placentae, and cysteine, methionine, and vitamin B6 metabolism pathways were among the most distinct signatures identified. These findings illustrate an altered placental morphology and metabolomic profile specific to uncomplicated MHO, offering new insights into how obesity without cardiometabolic complications influences fetoplacental growth and metabolism. They also represent a crucial first step towards marker identification for MHO pregnancies and underscore the importance of alternative care pathways when obesity is present but metabolic comorbidities are absent.

Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy represent two distinct cardiometabolic populations, each potentially necessitating alternative clinical management. However, the understanding of the unique physiological effects of uncomplicated MHO or MUO on fetoplacental growth and metabolism remains limited. This study aimed to identify changes in placental morphology and metabolites concerning maternal obesity, independent of pregnancy-related cardiometabolic complications. Placentae from women with a pre-pregnancy body mass index (BMI) 30 kg/m ² with no cardiometabolic diseases; n = 15) were analysed for indices of placental growth and untargeted metabolomics. Complementary measures of pro-inflammatory and antioxidant genes, as well as antioxidant proteins, enzymes, and lipid peroxidation markers were conducted. A clear placentomegaly without histopathological changes was observed in uncomplicated MHO pregnancies. The metabolite 3-aminoisobutanoic acid emerged as the top-ranked feature distinguishing MHO from control placentae, and cysteine, methionine, and vitamin B6 metabolism pathways were among the most distinct signatures identified. These findings illustrate an altered placental morphology and metabolomic profile specific to uncomplicated MHO, offering new insights into how obesity without cardiometabolic complications influences fetoplacental growth and metabolism. They also represent a crucial first step towards marker identification for MHO pregnancies and underscore the importance of alternative care pathways when obesity is present but metabolic comorbidities are absent.