Plasmalogen Deficiency and Overactive Fatty Acid Elongation Biomarkers in Serum of Breast Cancer Patients Pre- and Post-Surgery—New Insights on Diagnosis, Risk Assessment, and Disease Mechanisms

The polyunsaturated fatty acid (PUFA) elongase, ELOVL5, is upregulated in breast cancer (BC) vs. adjacent normal tissue. We performed a comprehensive lipid metabolomic analysis of serum using high-resolution accurate mass spectrometry from two case-control studies that included non-BC, BC subjects pre-surgery, and BC subjects one-month post-surgery to determine if the metabolic signatures of over-active fatty acid elongation and other lipid changes could be detected in BC vs. non-BC subjects: study 1 (n = 48: non-BC, n = 69: pre-surgery BC); study 2 (blinded validation: n = 121: non-BC, n = 62: pre-surgery BC, n = 31: one month post-surgery). The ratio of the ELOVL5 precursor, linoleic acid (18:2) to a non-ELOVL5 precursor, oleic acid (18:1) was evaluated in multiple lipid pools (phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), lyso-PtdCho, and free fatty acids). This ratio was lower in pre-surgery BC subjects in all pools in both studies (p < 0.001). At one-month post-surgery, the 18:2/18:1 ratios increased vs. pre-surgery and were no longer different from non-BC subjects (p > 0.05 expect for lyso-PtdCho). In contrast to the elongation biomarkers, docosahexaenoic acid (22:6n-3) containing ethanolamine plasmalogen (EtnPls) species were observed to be further decreased in BC subjects one-month post-surgery vs. pre-surgery levels (p < 0.001). These results are consistent with the hypothesis that ELOVL5 is upregulated in BC tissue, which would result in the selective depletion of 18:2 vs. 18:1 containing lipid species. Surgical removal of the tumor removes the overactive ELOVL5 effect on serum lipids. In contrast, the low EtnPls levels do not appear to be caused by BC tumor activity and may be pre-existent and a possible risk factor for BC. These results indicate that it may be possible to screen for both breast cancer risk and breast cancer activity using a simple blood test.

A Label-Free Proteomic Strategy to Investigate the Intramuscular fat Proteomic Differences Between Biceps Femoris and Longissimus Dorsi in Inner Mongolian Cashmere Goats

Background: As a major raw-cashmere-producing province in China. Nearly 700,000 Aerbasi cashmere goats are fed per year, and the corresponding meat production is nearly 10,000 tons. However, there are no reports on the meat of this goat. To better understand the molecular variations underlying intramuscular fat (IMF) anabolism and catabolism in Inner Mongolian cashmere goats, the proteomic differences between the biceps femoris (BF) and longissimus dorsi (LD) were investigated by a label-free strategy. Then, the identified proteins were verified as being involved in IMF anabolism and catabolism by Western blot analysis.Results: The IMF content was significantly higher in the BF than in the LD, suggesting that IMF accumulated more in the BF or was metabolized more in the LD. We performed proteomic analysis of IMF anabolism and catabolism at the proteomic level, and 1209 proteins were identified in the BF (high-IMF) and LD (low-IMF) groups. Among them, 110 were differentially expressed proteins (DEPs), 81 of which were upregulated in the high-IMF group, while 29 were upregulated in the low-IMF group. Gene ontology (GO) classification showed that the 110 DEPs were functionally classified into 100 annotation clusters. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the 110 DEPs covered 34 KEGG pathways. Three pathways were related to IMF metabolism and deposition—fatty acid metabolism, fatty acid degradation and fatty acid elongation—and included 7 proteins.Conclusion: GO and KEGG analyses showed that differentially expressed HADHA, HADHB, ACSL1, ACADS, ACAT1 and ACAA2 in the mitochondria act via fatty acid metabolism, fatty acid degradation and fatty acid elongation to influence the metabolism and synthesis of long-, short- and medium-chain fatty acids and modulate IMF anabolism and catabolism. Protein-protein interaction (PPI) network analysis showed that IMF accumulation in different muscle tissues of Inner Mongolian cashmere goats was affected not only by 5 key enzymes and proteins involved in fatty acid synthesis and metabolism but also by five DEPs (SUCLG1, SUCLG2, CS, DLST, and ACO2) in the TCA cycle. Our results provide new insights into IMF deposition in goats and improve our understanding of the molecular mechanisms underlying IMF anabolism and catabolism.

High Spatial-Resolution Imaging of the Dynamics of Cuticular Lipid Deposition During Arabidopsis Flower Development

ABSTRACTThe extensive collection of glossy (gl) and eceriferum (cer) mutants of maize and Arabidopsis have proven invaluable in dissecting the branched metabolic pathways that support cuticular lipid deposition. This branched pathway integrates the fatty acid elongation-decarbonylative branch and the fatty acid elongation-reductive branch that has the capacity to generate hundreds of cuticular lipid metabolites. In this study a combined transgenic and biochemical strategy was implemented to explore and compare the physiological function of three homologous genes, Gl2, Gl2-like and CER2 in the context of this branched pathway. These biochemical characterizations integrated new extraction-chromatographic procedures with high-spatial resolution mass spectrometric imaging methods to profile the cuticular lipids on developing floral tissues transgenically expressing these transgenes in wild-type or cer2 mutant lines of Arabidopsis. Collectively, these datasets establish that both the maize Gl2 and Gl2-like genes are functional homologs of the Arabidopsis CER2 gene. In addition, the dynamic distribution of cuticular lipid deposition follows distinct floral organ localization patterns indicating that the fatty acid elongation-decarbonylative branch of the pathway is differentially localized from the fatty acid elongation-reductive branch of the pathway.

Identification of potential biomarkers and inhibitors in SARS-CoV-2 infected macaques

The COVID-19 pandemic caused by the infection with SARS-CoV-2 has overwhelmed many health systems globally. Our study is to identify differentially expressed genes (DEGs) and the associated biological pathways of COVID-19 to elucidate the potential pathogenesis and metabolism. The gene expression profile of the GSE155363 dataset was originally produced using the high-throughput Illumina HiSeq 4000 (Macaca mulatta). Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed to discover their functional categories and biochemical pathways. The results suggested that four biological pathways: Fatty acid elongation, Biosynthesis of unsaturated fatty acids, Fatty acid metabolism, and Ribosome were mostly involved in the macaques with COVID-19. Thus, our study provides novel insights into the underlying pathogenesis of COVID-19.

Characteristics of Cuticular Wax and Analysis of Wax Biosynthesis Related Genes in Lanzhou Lily(Lilium Davidii Var. Unicolor) Under Drought Stress

Background: Plant wax is the general term of cuticle lipid components on the outer surface of plant tissue, which is closely related to drought resistance of plants. Lanzhou lily has the characteristics of wide adaptability, strong drought resistance, high ornamental and edible value. Plants were grown under three drought intensity treatments, namely, being watered at intervals of 5, 15, and 25 days. In this study, we analyzed the structure and component of cuticular wax of Lanzhou lily and Tresor under drought stress by scanning electron microscopy (SEM) and gas chromatography–mass spectrometry (GC-MS). We employed RNA sequencing (RNA-Seq) to investigate transcriptomic changes in the Lanzhou lily in response to drought stress.Results: In present study, the wax crystals of Lanzhou lily were mainly irregular flakes and filaments, while the wax crystals of Tresor lily were mainly granular. There were four kinds of compounds in the cuticle wax of Lanzhou lily and Tresor lily, which were acids, esters, alkanes and alcohols. Among them, the main components of Lanzhou lily were alkanes, and the content of acids in Tresor lily was more. Phylogenetic tree analysis showed that KCS homologous gene TRINITY_ DN101578_ c0_ g3 and TRINITY _ DN98845_ c1_ g2 genes were clustered into one group, TRINITY_ DN95975_ c0_ g3 and dicotyledons were clustered into the same branch. In addition, transcriptome analysis of Lanzhou lily showed that the metabolic pathway of fatty acid elongation was significant under severe drought stress. KCS1, KCS3, KCS6 and KCS11 encoding fatty acid elongation were significantly expressed under moderate drought stress. The expression of MYB96 transcription factor was only significant under severe drought stress. Conclusions: The wax content and components of Lanzhou lily were more than those of Tresor lily. Drought stress increased the wax content of Lanzhou lily and enhanced its drought resistance. Our research has revealed some important significant expression genes not only improved the drought tolerance of Lanzhou lily, but also had high application value in the development of drought tolerant varieties.

Cold-induced lipid dynamics and transcriptional programs in white adipose tissue

Background In mammals, cold exposure induces browning of white adipose tissue (WAT) and alters WAT gene expression and lipid metabolism to boost adaptive thermogenesis and maintain body temperature. Understanding the lipidomic and transcriptomic profiles of WAT upon cold exposure provides insights into the adaptive changes associated with this process. Results Here, we applied mass spectrometry and RNA sequencing (RNA-seq) to provide a comprehensive resource for describing the lipidomic or transcriptome profiles in cold-induced inguinal WAT (iWAT). We showed that short-term (3-day) cold exposure induces browning of iWAT, increases energy expenditure, and results in loss of body weight and fat mass. Lipidomic analysis shows that short-term cold exposure leads to dramatic changes of the overall composition of lipid classes WAT. Notably, cold exposure induces significant changes in the acyl-chain composition of triacylglycerols (TAGs), as well as the levels of glycerophospholipids and sphingolipids in iWAT. RNA-seq and qPCR analysis suggests that short-term cold exposure alters the expression of genes and pathways involved in fatty acid elongation, and the synthesis of TAGs, sphingolipids, and glycerophospholipids. Furthermore, the cold-induced lipid dynamics and gene expression pathways in iWAT are contrary to those previously observed in metabolic syndrome, neurodegenerative disorders, and aging, suggesting beneficial effects of cold-induced WAT browning on health and lifespan. Conclusion We described the significant alterations in the composition of glyphospholipids, glycerolipids, and sphingolipids and expression of genes involved in thermogenesis, fatty acid elongation, and fatty acid metabolism during the response of iWAT to short-term cold exposure. We also found that some changes in the levels of specific lipid species happening after cold treatment of iWAT are negatively correlated to metabolic diseases, including obesity and T2D.