Long-Term Mastication Changed Salivary Metabolomic Profiles.

Saliva is an ideal biofluid for monitoring oral and systemic health. Repeated mastication is a typical physical stimulus that improves salivary flow and oral hygiene. Recent metabolomic studies have shown the potential of salivary metabolomic components for various disease monitoring systems. Here, we evaluated the effect of long-term mastication on salivary metabolomic profiles. Young women with good oral hygiene (20.8 ± 0.3 years, n = 17) participated. They were prohibited from chewing gum during control periods (4 weeks each) and were instructed to chew a piece of gum base seven times a day for 10 min each time during the intervention period. Paired samples of unstimulated whole saliva collected on the last day of the control and intervention period were compared. Liquid chromatography−time-of-flight mass spectrometry successfully quantified 85 metabolites, of which 41 showed significant differences (p < 0.05, Wilcoxon paired test corrected by false discovery rate). Except for a few metabolites, such as citrate, most metabolites showed lower concentrations after the intervention. The pathways related to glycogenic amino acids, such as alanine, arginine, and glutamine, altered considerably. This study suggests that long-term mastication induces unstimulated salivary component-level changes.

Correlation of Plasma Amino Acid and Anthropometric Profiles with Brown Adipose Tissue Density in Humans.

This study examined the relationship between plasma amino acid (AA) concentrations, including branched-chain AAs, and brown adipose tissue density (BAT-d). One hundred and seventy-three subjects (69 men, 104 women) aged 22-68 years were recruited during the winter season. AAs were comprehensively quantified using liquid chromatography-time-of-flight-mass spectrometry. The total hemoglobin concentration in the supraclavicular region ([total-Hb]sup), an indicator of BAT-d, was assessed using near-infrared time-resolved spectroscopy. Anthropometric parameters, including age, percentage of body fat, and visceral fat, were evaluated. Factors associated with higher (≥74 µM) or lower (<74 µM) [total-Hb]sup were investigated by multiple logistic regression models that included AA concentrations alone (model 1) or AA concentrations and anthropometric parameters (model 2) as independent variables. When adjusted for the false discovery rate, [total-Hb]sup was positively correlated with glycine and asparagine levels in men and with the serine level in both men and women and was negatively correlated with the branched-chain AA concentration in men. Models 1 and 2 correlated with higher or lower BAT-d for men (r = 0.73, p = 0.015) and women (r = 0.58, p = 0.079) and for men (r = 0.82, p = 0.0070) and women (r = 0.70, p = 0.020), respectively. A combination of anthropometric parameters and plasma AA concentrations could be a reliable biomarker for higher and lower BAT-d.

Differential Tissue Metabolic Signatures in IgG4-Related Ophthalmic Disease and Orbital Mucosa-Associated Lymphoid Tissue Lymphoma.

Purpose: To identify tissue metabolomic profiles in biopsy specimens with IgG4-related ophthalmic disease (IgG4-ROD) and mucosa-associated lymphoid tissue (MALT) lymphoma and investigate their potential implication in the disease pathogenesis and biomarkers. Methods: We conducted a comprehensive analysis of the metabolomes and lipidomes of biopsy-proven IgG4-ROD (n = 22) and orbital MALT lymphoma (n = 21) specimens and matched adjacent microscopically normal adipose tissues using liquid chromatography time-of-flight mass spectrometry. The altered metabolomic profiles were visualized by heat map and principal component analysis. Metabolic pathway analysis was performed by Metabo Analyst 4.0 using differentially expressed metabolites. The diagnostic performance of the metabolic markers was evaluated using receiver operating characteristic curves. Machine learning algorithms were implemented by random forest using the R environment. Finally, an independent set of 18 IgG4-ROD and 17 orbital MALT lymphoma specimens were used to validate the identified biomarkers. Results: The principal component analysis showed a significant difference of both IgG4-ROD and orbital MALT lymphoma for biopsy specimens and controls. Interestingly, lesions in IgG4-ROD were uniquely enriched in arachidonic metabolism, whereas those in orbital MALT lymphoma were enriched in tricarboxylic acid cycle metabolism. We identified spermine as the best discriminator between IgG4-ROD and orbital MALT lymphoma, and the area under the receiver operating characteristic curve of the spermine to discriminate between the two diseases was 0.89 (95% confidence interval, 0.803-0.984). A random forest model incorporating a panel of five metabolites showed a high area under the receiver operating characteristic curve value of 0.983 (95% confidence interval, 0.981-0.984). The results of validation revealed that four tissue metabolites: N1,N12-diacetylspermine, spermine, malate, and glycolate, had statistically significant differences between IgG4-ROD and orbital MALT lymphoma with receiver operating characteristic values from 0.708 to 0.863. Conclusions: These data revealed the characteristic differences in metabolomic profiles between IgG4-ROD and orbital MALT lymphoma, which may be useful for developing new diagnostic biomarkers and elucidating the pathogenic mechanisms of these common orbital lymphoproliferative disorders.

Relationships between plasma lipidomic profiles and brown adipose tissue density in humans.

BACKGROUND/OBJECTIVES: The thermogenic function of brown adipose tissue (BAT) is generally activated in winter and tightly regulated through various metabolic processes. However, the mechanisms mediating these changes have not been elucidated in humans. Here, we investigated the relationships between BAT density (BAT-d) and lipid metabolites in plasma from men and women in the winter and summer. SUBJECTS/METHODS: In total, 92 plasma samples were obtained from 23 men and 23 women, aged 21-55 years, on two different occasions (summer and winter). Lipid metabolites were comprehensively quantified using liquid chromatography-time-of-flight-mass spectrometry. BAT-d was evaluated by measuring total hemoglobin concentrations in the supraclavicular region using near-infrared time-resolved spectroscopy. Anthropometric parameters, such as the percentage of whole body fat and visceral fat area (VFA), were evaluated. Factors influencing BAT-d were investigated by univariate and multivariate regression analyses. RESULTS: A variety of metabolite peaks, such as glycerophospholipids (168 peaks), steroids and derivatives (78 peaks), fatty acyls (62 peaks), and glycerolipids (31 peaks), were detected. Univariate regression analysis, corrected by false discovery rate to yield Q values, revealed significant correlations in BAT-d and phosphatidylethanolamine (PE(46:2), r = 0.62, Q = 4.9 × 10-2) in the summer, androgens (r = 0.75, Q = 7.0 × 10-3) in the winter, and diacylglycerol (DG(36:1), r = -0.68, Q = 4.9 × 10-2) in the summer in men, but not in women. Multivariate regression analysis in the winter revealed a significant correlation between BAT-d and plasma androgens (P = 5.3 × 10-5) in men and between BAT-d and VFA (P = 2.2 × 10-3) in women. CONCLUSIONS: Certain lipids in plasma showed unique correlations with BAT-d depending on sex and season. BAT-d showed a specific correlation with plasma androgens in men in the winter.