Traumatic acid inhibits ACSL4 associated lipid accumulation in adipocytes to attenuate high-fat diet-induced obesity.

Obesity is a major health concern that lacks effective intervention strategies. Traumatic acid (TA) is a potent wound-healing agent in plants, considered an antioxidant food ingredient. This study demonstrated that TA treatment significantly reduced lipid accumulation in human adipocytes and prevented high-fat diet induced obesity in zebrafish. Transcriptome sequencing revealed TA-activated fatty acid (FA) degradation and FA metabolism signaling pathways. Moreover, western blotting and quantitative polymerase chain reaction showed that TA inhibited the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Overexpression of ACSL4 resulted in the reversal of TA beneficiary effects, indicating that the attenuated lipid accumulation of TA was regulated by ACSL4 expression. Limited proteolysis-mass spectrometry and microscale thermophoresis were then used to confirm hexokinase 2 (HK2) as a direct molecular target of TA. Thus, we demonstrated the molecular basis of TA in regulating lipid accumulation and gave the first evidence that TA may function through the HK2-ACSL4 axis.

Differences in the metabolic profiles of brown and white adipocytes based on secretomics.

Brown adipocytes and white adipocytes play important roles in systemic metabolism and energy homeostasis. Recent studies have demonstrated that white adipocytes and brown adipocytes secrete numerous adipokines and thus act as endocrine cells. However, differences in the metabolites secreted from white adipocytes and brown adipocytes have never been reported. In this study, we assessed the metabolites secreted from white adipocytes and brown adipocytes. In total, the levels of 47 metabolites in brown adipocytes were significantly different from those in white adipocytes, with 31 high and 16 low in brown adipocytes as compared with those in white adipocytes. We classified these secreted metabolites as amino acids and peptides, fatty acids, and conjugates, glycerophosphocholines, furanones, and trichloroacetic acids. In addition, we identified the glycerophospholipid metabolism activated in white adipocytes, and these differentially expressed metabolites were associated with the mitogen-activated protein kinase pathway and Janus kinase-signal transducer and activator of transcription signaling pathway according to the Ingenuity Pathway Analysis (IPA) software analysis. This study revealed novel metabolites secreted from brown adipocytes and white adipocytes, and these metabolites from adipocytes may perform specific biological functions based on the type of adipocyte that secretes them, and this forms the material basis of the interaction between adipocytes and other cells.

Transcriptomics profiling reveal the heterogeneity of white and brown adipocyte.

The marker genes associated with white adipocytes and brown adipocytes have been previously identified; however, these markers have not been updated in several years, and the differentiation process of preadipocytes remains relatively fixed. Consequently, there has been a lack of exploration into alternative differentiation schemes. In this particular study, we present a transcriptional signature specific to brown adipocytes and white adipocytes. Notably, our findings reveal that ZNF497, ZIC1, ZFY, UTY, USP9Y, TXLNGY, TTTY14, TNNT3, TNNT2, TNNT1, TNNI1, TNNC1, TDRD15, SOX11, SLN, SFRP2, PRKY, PAX3KLHL40, PAX3, INKA2-AS1, SOX11, and TDRD15 exhibit high expression levels in brown adipocytes. XIST, HOXA10, PCAT19, HOXA7, PLSCR3, and AVPR1A exhibited high expression levels in white adipocytes, suggesting their potential as novel marker genes for the transition from white to brown adipocytes. Furthermore, our analysis revealed the coordinated activation of several pathways, including the PPAR signaling pathway, focal adhesion, retrograde endocannabinoid signaling, oxidative phosphorylation, PI3K-Akt signaling pathway, and thermogenesis pathways, in brown adipocytes. Moreover, in contrast to prevailing culture techniques, we conducted a comparative analysis of the differentiation protocols for white preadipocytes and brown preadipocytes, revealing that the differentiation outcome remained unaffected by the diverse culture schemes employed. However, the expression levels of certain marker genes in both adipocyte types were found to be altered. This investigation not only identified potential novel marker genes for adipocytes but also examined the impact of different differentiation methods on preadipocyte maturation. Consequently, these findings offer significant insights for further research on the differentiation processes of diverse adipocyte subtypes.

Methionine sulfoxide suppresses adipogenic differentiation by regulating the mitogen-activated protein kinase signaling pathway.

In this study, methionine sulfoxide (MetO) was identified as an active metabolite that suppresses adipogenesis after screening obese individuals versus the normal population. MetO suppressed the gene and protein expression of CCAAT/enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 4 (FABP4), and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) during human preadipocyte (HPA) differentiation. Adipogenesis decreased following MetO treatment; however, the preadipocyte number, proliferation, and apoptosis were unaffected. The activity of phosphorylated extracellular signal-related kinase (P-ERK) of the mitogen-activated protein kinase (MAPK) pathway was significantly inhibited in HPA after MetO treatment. Furthermore, treatment of preadipocytes with the selective P-ERK1/2 agonist Ro 67-7476 abolished the effect of MetO against adipogenesis suggesting that MetO function is dependent on the MAPK pathway. The mechanistic insights of adipogenesis suppression by MetO presented in this study shows its potential as an antiobesity drug.

Embryonic development, hatchling performance and metabolic profile after egg exposure to environmentally relevant levels of chlorpyrifos in an aquatic turtle.

The extensive use of organophosphorus insecticides poses a threat to the survival of non-target organisms. Ecotoxicological outcomes of embryonic exposure to insecticides are rarely evaluated in various oviparous species. In this study, soft-shelled turtle (Pelodiscus sinensis) eggs were incubated in moist substrate containing different levels (0, 2, 20 and 200 µg/kg) of chlorpyrifos to investigate its toxic effects on embryonic development and survival, and hatchling physiological performance. Chlorpyrifos exposure had no significant impacts on embryonic development rate and egg survival in P. sinensis. Similarly, embryonic chlorpyrifos exposure neither obviously affected the size and locomotor performance of hatchlings, nor changed the activities of superoxide dismutase and catalase, and content of malondialdehyde in their erythrocytes. Based on liquid chromatography-mass spectrometry analysis, minor metabolic perturbations related to amino acid, lipid and energy metabolism in hatchlings after embryonic chlorpyrifos exposure were revealed by hepatic metabolite profiling. Overall, our results suggested that embryonic exposure to environmentally relevant levels of chlorpyrifos had only a limited impact on physiological performances of hatchlings, although it would result in a potential risk of hepatotoxicity in P. sinensis.

Circular RNA circ-RCCD promotes cardiomyocyte differentiation in mouse embryo development via recruiting YY1 to the promoter of MyD88.

Congenital heart disease (CHD) is the most common birth defect, affecting approximately 1% of live births. Genetic and environmental factors are leading factors to CHD, but the mechanism of CHD pathogenesis remains unclear. Circular RNAs (circRNAs) are kinds of endogenous non-coding RNAs (ncRNAs) involved in a variety of physiological and pathological processes, especially in heart diseases. In this study, three significant differently expressed circRNA between maternal embryonic day (E) E13 and E17 was found by microarray assay. Among them, the content of circ-RCCD increases with the development of heart and was enriched in primary cardiomyocytes of different species, which arouses our attention. Functional experiments revealed that inhibition of circ-RCCD dramatically suppressed the formation of beating cell clusters, the fluorescence intensity of cardiac differentiation marker MF20, and the expression of the myocardial-specific markers CTnT, Mef2c, and GATA4. Next, we found that circ-RCCD was involved in cardiomyocyte differentiation through negative regulation of MyD88 expression. Further experiments proved that circ-RCCD inhibited MyD88 levels by recruiting YY1 to the promoter of MyD88; circ-RCCD inhibited nuclear translocation of YY1. These results reported that circ-RCCD promoted cardiomyocyte differentiation by recruiting YY1 to the promoter of MyD88. And, this study provided a potential role and molecular mechanism of circ-RCCD as a target for the treatment of CHD.

Associations between isoflavone exposure and reproductive damage in adult males: evidence from human and model system studies†.

It is controversial whether exposure to isoflavones exerts male reproductive toxicity. The aim of this study was to investigate whether isoflavone exposure during adulthood could have deleterious impacts on male reproductive health by the cross-sectional study, animal experiments, and in vitro tests. In the cross-sectional study, we observed that urinary isoflavones were not significantly associated with semen quality including sperm concentrations, sperm count, progressive motility, and total motility, respectively. However, negative associations were found between plasma testosterone and urinary Σisoflavones, genistein, glycitein, and dihydrodaidzein. In the animal experiments, serum and intratesticular testosterone levels were decreased in mice exposed to several dosages of genistein. Genistein administration caused upregulation of estrogen receptor alpha and downregulation of cytochrome P45017A1 protein levels in testes of mice. In vitro tests showed that genistein caused a concentration-dependent inhibition of testosterone production by TM3 Leydig cells. Elevated protein expression of estrogen receptor alpha and decreased messenger RNA/protein level of cytochrome P45017A1 were also observed in genistein-treated cells. Protein level of cytochrome P45017A1 and testosterone concentration were significantly restored in the estrogen receptor alpha small interferring RNA-transfected cells, compared to cells that treated with genistein alone. The results demonstrate that exposure to isoflavones during adulthood may be associated with alterations of reproductive hormones. Particularly, genistein, which inhibits testosterone biosynthesis through upregulation of estrogen receptor alpha in Leydig cells of mice, might induce the disruption of testosterone production in human. The present study provides novel perspective into potential targets for male reproductive compromise induced by isoflavone exposure.

Single-cell transcriptomes from turtle livers reveal sensitivity of hepatic immune cells to bacteria-infection.

The liver is important in the synthesis, metabolism and storage of nutrients, detoxification and immune response of the body, and the liver immune response against exogenous pathogens from the intestinal tract plays a key role in the immune activities. However, the cellular composition of the liver immune atlas remains sparsely studied in reptiles. We used single-cell RNA sequencing to identify the cellular profile of the liver of the Chinese soft-shelled turtle (Pelodiscus sinensis). We obtained the transcriptional landscape based on 9938 cells from the fractionation of fresh hepatic tissues from two individuals, uninfected and infected with bacteria (Aeromonas hydrophila). We identified seven hepatic immune cell subsets, including plasma, erythroid, T/NK, B, endothelial, dendritic and Kupffer cells. Bacteria-infection altered the number of liver immune cells, as revealed by the fact that the infected turtle had more plasma, endothelial and Kupffer cells and fewer T/NK, dendritic and erythroid cells than did the uninfected turtle. Our study is the first to provide a comprehensive view of the hepatic immune landscape of P. sinensis at the single-cell resolution that outlines the characteristics of immune cells in the turtle liver and provides a liver transcriptome baseline for turtle immunology.

[Expression of glucocorticoid receptor in prostate cancer and its clinical significance].

OBJECTIVE: To investigate the expression of glucocorticoid receptor (GR) in the PCa tissue and its correlation with the clinicopathological characteristics and prognosis of PCa. METHODS: Using immunohistochemical staining, we determined the expression of GR in the PCa tissue and analyzed its correlation with the clininicopathological features and prognosis of the malignancy. RESULTS: The positive expression of GR in the PCa tissue was 64%, of which the strongly positive rate was 34.7%. The GR expression was positively correlated with preoperative androgen-deprivation therapy (ADT) (χ2 = 22.307, P < 0.01), Gleason grades (χ2 = 16.534, P = 0.002) and clinical stages of the tumor (χ2 = 9.969, P = 0.041). Kaplan-Meier analysis showed that the GR expression was correlated not with the overall survival (P = 0.156), but with the PSA progression-free survival rate of the PCa patients (P = 0.042), with a shorter PSA progression-free survival time in those with a higher GR expression. Multivariate COX regression analysis revealed that the expression of GR was not an independent prognostic factor for PSA progression-free survival of the PCa patients. CONCLUSION: The expression of GR is related with preoperative ADT, and closely with the biological behavior of the malignancy and treatment resistance of the patients. GR is expected to be a new effective therapeutic target and a prognostic biomarker for PCa.

Venom-gland transcriptomic, venomic, and antivenomic profiles of the spine-bellied sea snake (Hydrophis curtus) from the South China Sea.

BACKGROUND: A comprehensive evaluation of the -omic profiles of venom is important for understanding the potential function and evolution of snake venom. Here, we conducted an integrated multi-omics-analysis to unveil the venom-transcriptomic and venomic profiles in a same group of spine-bellied sea snakes (Hydrophis curtus) from the South China Sea, where the snake is a widespread species and might generate regionally-specific venom potentially harmful to human activities. The capacity of two heterologous antivenoms to immunocapture the H. curtus venom was determined for an in-depth evaluation of their rationality in treatment of H. curtus envenomation. In addition, a phylogenetic analysis by maximum likelihood was used to detect the adaptive molecular evolution of full-length toxin-coding unigenes. RESULTS: A total of 90,909,384 pairs of clean reads were generated via Illumina sequencing from a pooled cDNA library of six specimens, and yielding 148,121 unigenes through de novo assembly. Sequence similarity searching harvested 63,845 valid annotations, including 63,789 non-toxin-coding and 56 toxin-coding unigenes belonging to 22 protein families. Three protein families, three-finger toxins (3-FTx), phospholipase A2 (PLA2), and cysteine-rich secretory protein, were detected in the venom proteome. 3-FTx (27.15% in the transcriptome/41.94% in the proteome) and PLA2 (59.71%/49.36%) were identified as the most abundant families in the venom-gland transcriptome and venom proteome. In addition, 24 unigenes from 11 protein families were shown to have experienced positive selection in their evolutionary history, whereas four were relatively conserved throughout evolution. Commercial Naja atra antivenom exhibited a stronger capacity than Bungarus multicinctus antivenom to immunocapture H. curtus venom components, especially short neurotoxins, with the capacity of both antivenoms to immunocapture short neurotoxins being weaker than that for PLA2s. CONCLUSIONS: Our study clarified the venom-gland transcriptomic and venomic profiles along with the within-group divergence of a H. curtus population from the South China Sea. Adaptive evolution of most venom components driven by natural selection appeared to occur rapidly during evolutionary history. Notably, the utility of commercial N. atra and B. multicinctus antivenoms against H. curtus toxins was not comprehensive; thus, the development of species-specific antivenom is urgently needed.

Serum matrix metalloproteinase-13 as a diagnostic biomarker for cutaneous squamous cell carcinoma.

BACKGROUND: A significant proportion of newly diagnosed patients with cutaneous squamous cell carcinoma (cSCC) have metastasis and eventually die of the disease, necessitating the exploration of novel biomarkers for early detection of cSCC aggressiveness, risk assessment and monitoring. Matrix metalloproteinase-13 (MMP-13) has been implicated in cSCC pathogenesis. Serum MMP-13 levels have been shown to predict survival in patients with esophageal SCC, but their diagnostic value for cSCC has not been explored. METHODS: We conducted a case-control study to examine serum MMP-13 as a biomarker for cSCC. Patients with cSCC undergoing surgical resection and health controls undergoing plastic surgery were recruited. ELISA for measurement of serum MMP-13 and immunohistochemistry for detection of tissue MMP-13 were performed, and the results were compared between the case and the control group, and among different patient groups. ROC curve analysis was performed to determine the diagnostic value of serum MMP-13 levels. RESULTS: The ratio of male to female, and the age between the case (n = 77) and the control group (n = 50) were not significantly different. Patients had significantly higher serum MMP-13 levels than healthy controls. Subjects with stage 3 cSCC had markedly higher serum MMP-13 levels than those with stage 1 and stage 2 cSCC. Patients with invasive cSCC had remarkably higher serum MMP-13 than those with cSCC in situ. Post-surgery serum MMP-13 measurement was done in 12 patients, and a significant MMP-13 decrease was observed after removal of cSCC. Tumor tissues had a remarkably higher level of MMP-13 than control tissues. Serum MMP-13 predicted the presence of invasive cSCC with an AUC of 0.87 (95% CI [0.78 to 0.95]) for sensitivity and specificity of 81.7 and 82.4%, respectively for a cut-off value of 290 pg/mL. Serum MMP-13 predicted lymph node involvement with an AUC of 0.94 (95% CI [0.88 to 0.99]) for sensitivity and specificity of 93.8 and 88.5%, respectively for a cut-off value of 430 pg/mL. CONCLUSION: Serum MMP-13 might serve as a valuable biomarker for early detection of cSCC invasiveness and monitoring of cSCC progression.

Correction to: Functional analysis of GhCHS, GhANR and GhLAR in colored fiber formation of Gossypium hirsutum L.

In the original publication of this article [1], the authors pointed out the Fig. 4b was same with Fig. 4c. The correct Fig. 4b should be below.

Functional analysis of GhCHS, GhANR and GhLAR in colored fiber formation of Gossypium hirsutum L.

BACKGROUND: The formation of natural colored fibers mainly results from the accumulation of different anthocyanidins and their derivatives in the fibers of Gossypium hirsutum L. Chalcone synthase (CHS) is the first committed enzyme of flavonoid biosynthesis, and anthocyanidins are transported into fiber cells after biosynthesis mainly by Anthocyanidin reductase (ANR) and Leucoanthocyanidin reductase (LAR) to present diverse colors with distinct stability. The biochemical and molecular mechanism of pigment formation in natural colored cotton fiber is not clear. RESULTS: The three key genes of GhCHS, GhANR and GhLAR were predominantly expressed in the developing fibers of colored cotton. In the GhCHSi, GhANRi and GhLARi transgenic cottons, the expression levels of GhCHS, GhANR and GhLAR significantly decreased in the developing cotton fiber, negatively correlated with the content of anthocyanidins and the color depth of cotton fiber. In colored cotton Zongxu1 (ZX1) and the GhCHSi, GhANRi and GhLARi transgenic lines of ZX1, HZ and ZH, the anthocyanidin contents of the leaves, cotton kernels, the mixture of fiber and seedcoat were all changed and positively correlated with the fiber color. CONCLUSION: The three genes of GhCHS, GhANR and GhLAR were predominantly expressed early in developing colored cotton fibers and identified to be a key genes of cotton fiber color formation. The expression levels of the three genes affected the anthocyanidin contents and fiber color depth. So the three genes played a crucial part in cotton fiber color formation and has important significant to improve natural colored cotton quality and create new colored cotton germplasm resources by genetic engineering.

Semen Quality in Chinese College Students: Associations With Depression and Physical Activity in a Cross-Sectional Study.

OBJECTIVE: Behavioral and psychosocial factors have been associated with a decline of the quality of semen. However, the relationship of depression and physical activity (PA) with semen quality remains unclear. METHODS: Data were obtained from 587 young male Chinese college students in June 2013. Participants completed a questionnaire assessing life-style factors, the Zung self-rated depression scale, and three items related to PA. They underwent a physical examination and provided a semen sample and a blood sample for reproductive hormones (testosterone, estrogen, progesterone, follicle-stimulating hormone, luteinizing hormone, and prolactin). RESULTS: Men with high depression scores (n = 63, 10.7%) had lower sperm concentration (M (SD) = 66.9 (74.5) versus 72.6 (56.9) [10/ml], p = .043) and total sperm count (M (SD) = 241.6 (299.7) versus 257.0 (204.0) [10], p = .024) than nondepressed men. Participants with low PA levels (n = 99, 16.9%) had lower total sperm count (M (SD) = 204.4 (153.7) versus 265.8 (225.8) [10/ml], p = .017) than participants with higher activity levels. After adjusting for potential confounders, depressed men had 18.90% (95% confidence interval [CI] = 1.14%-33.47%) lower sperm concentration and 21.84% (95% CI = 3.39%-36.90%) lower total sperm count than nondepressed men. Men with low PA levels had 23.03% (95% CI = 2.80%-46.89%) lower total sperm count than physically active participants. An interaction effect between depression and PA on sperm concentration was detected (p = .033). There were no significant associations of depression and PA with reproductive hormones (p > .05). CONCLUSIONS: Depression and low levels of PA are associated with lower levels of semen quality, which may have implications for reproductive health.

Does the oviparity-viviparity transition alter the partitioning of yolk in embryonic snakes?

BACKGROUND: The oviparity-viviparity transition is a major evolutionary event, likely altering the reproductive process of the organisms involved. Residual yolk, a portion of yolk remaining unutilized at hatching or birth as parental investment in care, has been investigated in many oviparous amniotes but remained largely unknown in viviparous species. Here, we used data from 20 (12 oviparous and 8 viviparous) species of snakes to see if the oviparity-viviparity transition alters the partitioning of yolk in embryonic snakes. We used ANCOVA to test whether offspring size, mass and components at hatching or birth differed between the sexes in each species. We used both ordinary least squares and phylogenetic generalized least squares regressions to test whether relationships between selected pairs of offspring components were significant. We used phylogenetic ANOVA to test whether offspring components differed between oviparous and viviparous species and, more specifically, the hypothesis that viviparous snakes invest more in the yolk as parental investment in embryogenesis to produce more well developed offspring that are larger in linear size. RESULTS: In none of the 20 species was sex a significant source of variation in any offspring component examined. Newborn viviparous snakes on average contained proportionally more water and, after accounting for body dry mass, had larger carcasses but smaller residual yolks than did newly hatched oviparous snakes. The rates at which carcass dry mass (CDM) and fat body dry mass (FDM) increased with residual yolk dry mass (YDM) did not differ between newborn oviparous and viviparous snakes. Neither CDM nor FDM differed between newborn oviparous and viviparous snakes after accounting for YDM. CONCLUSIONS: Our results are not consistent with the hypothesis that the partitioning of yolk between embryonic and post-embryonic stages differs between snakes that differ in parity mode, but instead show that the partitioning of yolk in embryonic snakes is species-specific or phylogenetically related. We conclude that the oviparity-viviparity transition does not alter yolk partitioning in embryonic snakes.

The effect of two cryopreservation methods on human sperm DNA damage.

Several methods are currently available for selection when conducting sperm cryopreservation, however, these methods might cause different degrees of damage on sperm DNA. The aim of the this study is to compare the effects of storage at -80 °C (in ultra-low temperature refrigerator) and at -196 °C (in liquid nitrogen) on sperm DNA damage, thus to provide a reference for choosing the right method according to different aims. We randomly collected 28 semen samples from college students of Chongqing city. The samples stored at -80 °C were neat semen samples and the samples stored at -196 °C were mixed with additional cryoprotectants. Each sample was subjected to two freezing-thawing cycles, and the sperm DNA damage levels of fresh and thawed samples were measured by single cell gel electrophoresis (SCGE) and sperm chromatin structure assay (SCSA). Both SCGE and SCSA assays showed cryopreservation induced significant damage to sperm DNA. However, storage at -196 °C lead to more severe damage to sperm DNA than storage at -80 °C measured by SCSA. Sperm DNA damage increased simultaneously with the higher frequency of freezing-thawing cycles. We concluded that storage of neat semen samples at -80 °C had milder damage to sperm DNA than storage at -196 °C mixed with cryoprotectants. To avoid additional sperm DNA damage, repeated freezing and thawing should be prevented.

Atorvastatin treatment improves effects of implanted mesenchymal stem cells: meta-analysis of animal models with acute myocardial infarction.

BACKGROUND: Previous studies reported that Atorvastatin (ATOR) can improve the efficacy of Mesenchymal stem cells (MSCs) transplantation after acute myocardial infarction (AMI). However, the results of those studies were inconsistent. To clarify the beneficial effects of atorvastatin added to the cell therapy with MSCs in animal model of acute myocardial infarction (AMI), we performed a systematic review and meta-analysis of case-control studies. METHODS: Searches were performed using the PubMed database, the Excerpta Medica Database (Embase), the Science Citation Index, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search term included "Atorvastatin (or Ator)", "Mesenchymal Stem Cells (or Mesenchymal Stem Cell or MSC or MSCs)" and "Acute Myocardial Infarction (or Myocardial Infarction or AMI or MI)". The endpoints were the left ventricular ejection fraction (LVEF) in animal model with AMI. RESULTS: In total, 5 studies were included in the meta-analysis. Pooled analysis indicated a significant LVEF difference at 4 weeks follow-up between MSCs + ATOR combine group and MSCs alone group (95 % CI, 9.09-13.62 %; P < 0.01) with heterogeneity (P = 0.28; P >0.05) and inconsistency (I(2): 22 %). CONCLUSIONS: Atorvastatin can enhance the existing effects of MSCs transplantation, and this combinational therapy is a superior cell/pharmacological therapeutic approach that merits future preclinical and clinical studies.

Metabolomic analysis reveals macrophage metabolic reprogramming and polarization under different nutritional cues.

BACKGROUND AND AIMS: Obesity-induced chronic inflammation and metabolic abnormalities are highly relevant to the functional dysregulation of macrophages, especially under obese conditions. Hyperglycemia and hyperlipidemia, central to obesity, directly alter macrophage activity. However, the impacts of different nutritional cues on the intricate metabolic networks in macrophages remain unclear. MATERIALS AND METHODS: In this study, we employed metabolomic approaches to examine the metabolic responses of macrophages to high glucose, high fat and their coexistence, aiming to delineate the molecular mechanisms of nutritional factors on macrophage activation and obesity-related diseases from a metabolic perspective. RESULTS: Our findings revealed that different nutritional conditions could reprogram key metabolism in macrophages. Additionally, we identified a metabolite derived from macrophages, Long-Chain Phosphatidylcholine (LPC), which exerts beneficial effects on obese mice. It ameliorates the obesity phenotype and improves glucose metabolism profiles. This discovery suggests that LPC has a significant therapeutic potential in the context of obesity-induced metabolic dysfunctions. Our study unveils the metabolic phenotype of macrophages in high-fat and high-sugar environments and uncovers a macrophage-derived metabolite that significantly ameliorates the obesity phenotype. CONCLUSION: This finding reveals a potential dialogue mechanism between macrophages and adipocytes, shedding light on the complex interplay of immune and metabolic systems in obesity. This discovery not only enhances our understanding of obesity's underlying mechanisms but also opens up new avenues for therapeutic interventions targeting macrophage-adipocyte interactions.

Anti-adipogenesis effect of indole-3-acrylic acid on human preadipocytes and HFD-induced zebrafish.

BACKGROUND: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people's quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity. AIMS: However, whether the downstream catabolite of tryptophan, 3-indole acrylic acid (IA), is involved in obesity remains unclear. METHODS: We collected the samples of serum from peripheral blood of obesity and health controls, and liquid chromatography-mass spectrometry (LC-MS) was performed to identify the plasma levels of IA. Additionally, we verified the potential benefits of IA on human preadipocytes and HFD- induced zebrafish by cell viability assay, flow cytometry assay, Oil red O staining, total cholesterol (T-CHO), triglyceride (TG) and nonesterified free fatty acids (NEFA) measurements and Nile Red staining. RNA-Seq, functional analysis and western blot revealed the mechanisms underlying the function of IA. RESULTS: We found that the content of IA in peripheral blood serum of overweight people was significantly lower than that of normal people. In addition, supplementation with IA in zebrafish larvae induced by a high fat diet (HFD) dramatically reduced HFD induced lipid accumulation. IA had no effect on proliferation and apoptosis of preadipocytes, but significantly inhibited adipogenesis of preadipocytes by down-regulate CEBPα and PPARγ. RNA-Seq and functional analysis revealed that IA regulated the adipogenesis of preadipocytes through stimulate the phosphorylation of STAT1. CONCLUSIONS: Taken together, IA has been identified as a potent metabolite for the prevention or treatment of obesity.

Study on pulp metabolism of patients with pulpitis using ultra-performance liquid chromatography coupled with Orbitrap mass spectrometry.

BACKGROUND AND AIMS: Pulpitis, a pulp disease caused by caries, trauma, and other factors, has a high clinical incidence. This study focused on identifying possible metabolic biomarkers of pulpitis cases and analyzing the related metabolic pathways for providing a theoretical foundation to diagnose and prevent pulpitis. MATERIALS AND METHODS: Pulp samples from 20 pulpitis cases together with 20 normal participants were analyzed with a serum metabolomics approach using ultra-high-performance liquid chromatography (UPLC)/Orbitrap mass spectrometry. Moreover, this work carried out multivariate statistical analysis for screening potential biomarkers of pulpitis. RESULTS: Through biomarker analysis and identification, such as partial least squares discrimination analysis, orthogonal partial least squares discriminant analysis model establishment, correlation analysis, and biomarker pathway analysis, 40 biomarkers associated with 20 metabolic pathways were identified, including 20 upregulated and 20 downregulated metabolites. Those major biomarkers included oxoglutaric acid, inosine, citric acid, and PA(14:1(9Z)/PGD1). Among them, oxoglutaric acid and inosine were most significantly downregulated and had the highest correlation with pulpitis. Among these metabolic pathways, GABAergic synapse and alanine, aspartate, and glutamate metabolism were positively correlated with pulpitis. 4. CONCLUSIONS: These biomarkers as well as metabolic pathways may offer the theoretical foundation to understand pulpitis pathogenesis and develop preventive drugs.