Biosynthesis Of Unsaturated Fatty Acids Research Articles

Plasma metabolites associated with physiological and biochemical indexes indicate the effect of caging stress on mallard ducks (Anas platyrhynchos).

ObjectiveCage rearing has critical implications for the laying duck industry because it is convenient for feeding and management. However, caging stress is a type of chronic stress that induces maladaptation. Environmental stress responses have been extensively studied, but no detailed information is available about the comprehensive changes in plasma metabolites at different stages of caging stress in ducks. We designed this experiment to analyze the effects of caging stress on performance parameters and oxidative stress indexes in ducks.MethodsLiquid chromatography tandem mass spectrometry (LC/MS-MS) was used to determine the changes in metabolites in duck plasma at 5 (CR5), 10 (CR10), and 15 (CR15) days after cage rearing and traditional breeding (TB). The associated pathways of differentially altered metabolites were analyzed using Kyoto encyclopedia of genes and genomes (KEGG) database.ResultsThe results of this study indicate that caging stress decreased performance parameters, and the plasma total superoxide dismutase levels were increased in the CR10 group compared with the other groups. In addition, 1,431 metabolites were detected. Compared with the TB group, 134, 381, and 190 differentially produced metabolites were identified in the CR5, CR10, and CR15 groups, respectively. The results of principal component analysis (PCA) show that the selected components sufficiently distinguish the TB group and CR10 group. KEGG analysis results revealed that the differentially altered metabolites in duck plasma from the CR5 and TB groups were mainly associated with ovarian steroidogenesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism.ConclusionIn this study, the production performance, blood indexes, number of metabolites and PCA were compared to determine effect of the caging stress stage on ducks. We inferred from the experimental results that caging-stressed ducks were in the sensitive phase in the first 5 days after caging, caging for approximately 10 days was an important transition phase, and then the duck continually adapted.

Environmental decomposition and remodeled phytotoxicity of framework-based nanomaterials

Zeolitic imidazole frameworks (ZIFs) have attracted a considerable amount of attention for use in environmental applications (e.g., pollutant adsorption and photocatalysis in water treatments). The environmental stability and toxicity of ZIFs are key prerequisites for their practical applications, but information about these factors is largely lacking. The present work finds that pristine ZIFs (ZIF-8 and ZIF-67) photodegrade from frame structures into two-dimensional nanosheets and are oxidized to zinc carbonate (ZIF-8) and Co3O4 (ZIF-67) under visible-light irradiation. The photoinduced electrons, holes and free radicals promote dissolution of the metal cores and organic ligands, leading to collapse of the frame structure. The photodegradation of ZIF-8 alleviates developmental inhibition, oxidative stress, plasmolysis, and photosynthetic toxicity, while the photodegradation of ZIF-67 aggravates nanotoxicity. The integration of metabolomics and transcriptomics analysis reveals that unsaturated fatty acid biosynthesis and metal ion-binding transcription contribute to the altered toxicity of ZIF photodegradation. These findings highlight the roles of photodegradation in structural transformation and alteration of the toxicity of ZIFs, alarming the study of pristine metal-organic frameworks (MOFs).

A transcriptome analysis focusing on growth performance and lipid metabolism‐related genes of grass carp ( Ctenopharyngodon idella ) fed with tea polyphenols basal diets

Several studies have highlighted the effect of Tea polyphenol (TPs) on growth performance and the gene regulation associated with the metabolic pathway and of various species. However, there is less information about the effect of TPs on growth performance and the regulation of genes related to the metabolic pathway of Grass carp (Ctenopharyngodon idellus). Six diets with different TPs level (0, 250, 500, 1,000, 2,000 and 4,000 mg/kg) were formulated. Result found that TPs increased the feed conversion efficiency (FCE) at different levels, and the highest FCE and specific growth rate (SGR) (p < 0.05) were achieved by the 500 mg/kg in the TPs group. Additionally, transcriptome sequencing of control and TPs groups was performed, and numerous differentially expressed genes (DEGs) were determined in the metabolic pathway of grass carp. The differentially expressed genes were validated by the qRT-PCR technique. DEGs were associated with arachidonic acid metabolism, linoleic acid metabolism, alpha-linolenic acid metabolism, biosynthesis of unsaturated fatty acids, fatty acid biosynthesis and fatty acid degradation. Our findings could provide new insight into the effect of TPs on growth performance and the regulation of genes associated with the metabolic pathway of grass carp.

Untargeted Metabolomics Analysis Revealed Lipometabolic Disorders in Perirenal Adipose Tissue of Rabbits Subject to a High-Fat Diet.

Simply SummaryA high-fat diet is widely recognized as a significant modifiable risk for metabolic diseases. In this study, untargeted metabolomics, combined with liquid chromatography and high-resolution mass spectrometry, was used to evaluate perirenal adipose tissue metabolic changes. Our study revealed 206 differential metabolites. These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids, the arachidonic acid metabolic pathway, the ovarian steroidogenesis pathway, and the platelet activation pathway. Our study revealed that a high-fat diet causes significant lipometabolic disorders; these metabolites may inhibit oxygen respiration by increasing adipocytes cells and density, cause mitochondrial and endoplasmic reticulum dysfunction, produce inflammation, and finally lead to insulin resistance, thereby increasing the risk of Type 2 diabetes, atherosclerosis, and other metabolic syndromes.A high-fat diet (HFD) is widely recognized as a significant modifiable risk for insulin resistance, inflammation, Type 2 diabetes, atherosclerosis and other metabolic diseases. However, the biological mechanism responsible for key metabolic disorders in the PAT of rabbits subject to HFD remains unclear. Here, untargeted metabolomics (LC-MS/MS) combined with liquid chromatography (LC) and high-resolution mass spectrometry (MS) were used to evaluate PAT metabolic changes. Histological observations showed that the adipocytes cells and density of PAT were significantly increased in HFD rabbits. Our study revealed 206 differential metabolites (21 up-regulated and 185 down-regulated); 47 differential metabolites (13 up-regulated and 34 down-regulated), comprising mainly phospholipids, fatty acids, steroid hormones and amino acids, were chosen as potential biomarkers to help explain metabolic disorders caused by HFD. These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids, the arachidonic acid metabolic pathway, the ovarian steroidogenesis pathway, and the platelet activation pathway. Our study revealed that a HFD caused significant lipometabolic disorders. These metabolites may inhibit oxygen respiration by increasing the adipocytes cells and density, cause mitochondrial and endoplasmic reticulum dysfunction, produce inflammation, and finally lead to insulin resistance, thus increasing the risk of Type 2 diabetes, atherosclerosis, and other metabolic syndromes.

Integration of miRNAs, Degradome, and Transcriptome Omics Uncovers a Complex Regulatory Network and Provides Insights Into Lipid and Fatty Acid Synthesis During Sesame Seed Development.

Sesame (Sesamum indicum L.) has always been known as a health-promoting oilseed crop because of its nutrient-rich oil. In recent years, studies have focused on lipid and fatty acid (FA) biosynthesis in various plants by high-throughput sequencing. Here, we integrated transcriptomics, small RNAs, and the degradome to establish a comprehensive reserve intensive on key regulatory micro RNA (miRNA)-targeting circuits to better understand the transcriptional and translational regulation of the oil biosynthesis mechanism in sesame seed development. Deep sequencing was performed to differentially express 220 miRNAs, including 65 novel miRNAs, in different developmental periods of seeds. GO and integrated KEGG analysis revealed 32 pairs of miRNA targets with negatively correlated expression profiles, of which 12 miRNA-target pairs were further confirmed by RT-PCR. In addition, a regulatory co-expression network was constructed based on the differentially expressed gene (DEG) profiles. The FAD2, LOC10515945, LOC105161564, and LOC105162196 genes were clustered into groups that regulate the accumulation of unsaturated fatty acid (UFA) biosynthesis. The results provide a unique advanced molecular platform for the study of lipid and FA biosynthesis, and this study may serve as a new theoretical reference to obtain increased levels of UFA from higher-quality sesame seed cultivars and other plants.

Changes in plasma and urine metabolites associated with empagliflozin in patients with type 1 diabetes.

To examine the impact of the sodium-glucose co-transporter-2 inhibitor, empagliflozin, on plasma and urine metabolites in participants with type 1 diabetes. Participants (n=40, 50% male, mean age 24.3 years) with type 1 diabetes and without overt evidence of diabetic kidney disease had baseline assessments performed under clamped euglycaemia and hyperglycaemia, on two consecutive days. Participants then proceeded to an 8-week, open-label treatment period with empagliflozin 25 mg/day, followed by repeat assessments under clamped euglycaemia and hyperglycaemia. Plasma and urine metabolites were first grouped into metabolic pathways using MetaboAnalyst software. Principal component analysis was performed to create a representative value for each sufficiently represented metabolic group (false discovery rate ≤ 0.1) for further analysis. Of the plasma metabolite groups, tricarboxylic acid (TCA) cycle (P < .0001), biosynthesis of unsaturated fatty acids (P=.0045), butanoate (P < .0001), propanoate (P=.0053), and alanine, aspartate and glutamate (P < .0050) metabolites were increased after empagliflozin treatment under clamped euglycaemia. Of the urine metabolite groups, only butanoate metabolites (P=.0005) were significantly increased. Empagliflozin treatment also attenuated the increase in a number of urine metabolites observed with acute hyperglycaemia. Empagliflozin was associated with increased lipid and TCA cycle metabolites in participants with type 1 diabetes, suggesting a shift in metabolic substrate use and improved mitochondrial function. These effects result in more efficient energy production and may contribute to end-organ protection by alleviating local hypoxia and oxidative stress.

A UPLC-MS/MS-based metabolomics analysis of the pharmacological mechanisms of rabdosia serra against cholestasis

BackgroundRabdosia Serra, the dried aerial parts of Rabdosia serra (Maxim.) Hara (RS) from the Labiatae family, is a traditional Chinese herbal medicine called Xihuangcao. Although RS has been found to exert a therapeutic effect on cholestasis, the underlying molecular mechanism remains unclear. PurposeThis study was designed to investigate the pharmacological effect and mechanism of RS on cholestatic rats using metabolomics platform. MethodsHistopathology and biochemical evaluations were performed to determine the therapeutic effect of RS and developed a rapid metabolite detection technology method based on UPLC-MS/MS to perform metabolomics research. Further, quantitative real-time polymerase chain reaction (RT-qPCR) was used to study the effect of RS on the bile acid metabolism pathway at the transcriptional level. ResultsRS significantly reduced the bile flow rates in cholestatic rats and decreased the levels of ALT, AST, TBA, T-BIL, and LDH, which were increased in the model group. Histological analysis showed that RS alleviated the liver injury induced by ANIT. Serum metabolomics results revealed 33 of the 37 biomarkers were found to be significantly altered by ANIT, and 26 were considerably changed following treatment with RS. Metabolic pathway analysis revealed four pathways such as primary bile acid biosynthesis, biosynthesis of unsaturated fatty acids, and arachidonic acid and tryptophan metabolism. The bile acid secretion process and the inflammation and oxidative stress processes are the major biochemical reactions following treatment with ANIT and RS. Bile acid-targeted metabolomics study showed that TCA, GCA, GCDCA, and GDCA might be sensitive biomarkers that induced liver injury. we found that treatment with RS regulated the levels of bile acid in the serum and liver and restored the proportion of bile acids, especially CA and conjugated bile acids, such as TCA and GCA, in the bile duct. RS increased the mRNA expression levels of FXR, SHP, BSEP, and MRP2 in livers, and IBABP, OST-α, and OST-β in the ileum. Conclusion: In this study, RS was found to protect the liver by regulating multiple metabolic pathways and promoting the excretion of bile acids. Simultaneously, RS played an essential role in reversing the imbalance of bile acids and protected against cholestasis by regulating the expression of transporters associated with bile acids. We demonstrated the correlation between molecular mechanisms and metabolites, provide a reference for the fabrication of extracts that can be used to treat cholestasis.

Omics Multi-Layers Networks Provide Novel Mechanistic and Functional Insights Into Fat Storage and Lipid Metabolism in Poultry.

Fatty acid metabolism in poultry has a major impact on production and disease resistance traits. According to the high rate of interactions between lipid metabolism and its regulating properties, a holistic approach is necessary. To study omics multilayers of adipose tissue and identification of genes and miRNAs involved in fat metabolism, storage and endocrine signaling pathways in two groups of broiler chickens with high and low abdominal fat, as well as high-throughput techniques, were used. The gene–miRNA interacting bipartite and metabolic-signaling networks were reconstructed using their interactions. In the analysis of microarray and RNA-Seq data, 1,835 genes were detected by comparing the identified genes with significant expression differences (p.adjust < 0.01, fold change ≥ 2 and ≤ −2). Then, by comparing between different data sets, 34 genes and 19 miRNAs were detected as common and main nodes. A literature mining approach was used, and seven genes were identified and added to the common gene set. Module finding revealed three important and functional modules, which were involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, biosynthesis of unsaturated fatty acids, Alzheimer’s disease metabolic pathway, adipocytokine, insulin, PI3K–Akt, mTOR, and AMPK signaling pathway. This approach revealed a new insight to better understand the biological processes associated with adipose tissue.

Seed specifically over-expressing DGAT2A enhances oil and linoleic acid contents in soybean seeds

Triacylglycerol (TAG), a main component of oil, is mainly biosynthesized by diacylglycerol acyltransferase (DGAT), which is critical for oil accumulation in plants. Intensive focus has been on DGAT2 functioning in unsaturated fatty acids biosynthesis. In this study, we analyzed the coding sequence (CDS) and amino acid sequence of GmDGAT2A and determined its key active sites through site-directed mutagenesis. As a consequence, H132, G201, and P152-X-I154-K155 were found to be essential active sites for GmDGAT2A. The spatial structure of the protein may bring the three active sites into close proximity, constituting an active domain. Additionally, N-terminus of GmDGAT2A was found to be an important regulator for the activity. Further, in vitro activity results uncovered GmDGAT2A was prone to utilize C18:2-CoA as the substrate. Consequently, overexpression of GmDGAT2A driven by a seed-specific promoter of Gmole1 in soybean significantly increased linoleic acid content specifically and total oil content, concomitant with accelerated elongation.

Integrated lipidomics and proteomics reveal cardiolipin alterations, upregulation of HADHA and long chain fatty acids in pancreatic cancer stem cells

Pancreatic cancer stem cells (PCSCs) play a key role in the aggressiveness of pancreatic ductal adenocarcinomas (PDAC); however, little is known about their signaling and metabolic pathways. Here we show that PCSCs have specific and common proteome and lipidome modulations. PCSCs displayed downregulation of lactate dehydrogenase A chain, and upregulation of trifunctional enzyme subunit alpha. The upregulated proteins of PCSCs are mainly involved in fatty acid (FA) elongation and biosynthesis of unsaturated FAs. Accordingly, lipidomics reveals an increase in long and very long-chain unsaturated FAs, which are products of fatty acid elongase-5 predicted as a key gene. Moreover, lipidomics showed the induction in PCSCs of molecular species of cardiolipin with mixed incorporation of 16:0, 18:1, and 18:2 acyl chains. Our data indicate a crucial role of FA elongation and alteration in cardiolipin acyl chain composition in PCSCs, representing attractive therapeutic targets in PDAC.

Lipidomic profiling of the developing kernel clarifies the lipid metabolism of Paeonia ostii

Lipid components in the developing kernel of Paeonia ostii were determined, and the fatty acid (FA) distributions in triacylglycerol and phospholipids were characterized. The lipids in the kernel were mainly phospholipids (43%), neutral glycerides (24%), fatty acyls (26%), and sphingolipids (4.5%). The dominant neutral glycerides were TAG and diacylglycerol. The PL components included phosphatidic acid, phosphatidyl glycerol, phosphatidyl choline, phosphatidyl serine, phosphatidyl inositol, and phosphatidyl ethanolamine. As the kernel developed, the profiles of the molecular species comprising TAG and PL changed, especially during the earlier phases of oil accumulation. During rapid oil accumulation, the abundances of sphingosine-1-phosphate, pyruvic acid, stearic acid, and alpha-linolenic acid changed significantly; the sphingolipid metabolism and unsaturated FAs biosynthesis pathways were significantly enriched in these differentially abundant metabolites. Our results improve our understanding of lipid accumulation in tree peony seeds, and provide a framework for the analysis of lipid metabolisms in other oil crops.

The analysis of the effects of Liuwei Dihuang decoction on aging-related metabolites and metabolic pathways in naturally aging mice by ultra-performance liquid chromatography quadruple time-of-light mass spectrometry.

Liuwei Dihuang decoction (LWDH) has been used to treat age-related diseases in Asia for thousands of years. Its effect is significant, but the mechanism is not entirely understood. The development and maturity of metabonomics technology have created a new way to understand its effects. In this study, 20-month-old naturally aging mice were used as the research subjects. Mice were randomly divided into the young group, elderly group, vitamin E group, and LWDH group, with 10 mice in each group. The UPLC-Q-TOF-MS technique analyzed the changes in plasma metabolism of these mice. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to study metabolic markers and metabolic pathways. Compared with the elderly group, the organ index and weightbearing swimming time of the LWDH and vitamin E groups increased (P ≤ 0.01). The results show that LWDH can benignly regulate the expression level of 11 aging-associated metabolites in aged mice and alleviate the aging state of mice. These metabolites mainly affect the metabolism of glutathione, unsaturated fatty acid biosynthesis, pyrimidine, selenium, pentose phosphate, arginine, and proline.

Lipid accumulation of Chlorella sp. TLD6B from the Taklimakan Desert under salt stress.

Chlorella has become an important raw material for biodiesel production in recent years, and Chlorella sp. TLD6B, a species with high lipid concentrations and high salt and drought tolerance, has been cultivated on a large scale. To explore the lipid accumulation of Chlorella sp. TLD6B and its relationship to external NaCl concentrations, we performed physiological measurements and genome-wide gene expression profiling under different levels of salt stress. Chlorella sp. TLD6B was able to tolerate high levels of salt stress (0.8 M NaCl addition). Lipid concentrations initially increased and then decreased as salt stress increased and were highest under the addition of 0.2 M NaCl. Comparative transcriptomic analysis revealed that salt stress enhanced the expression of genes related to sugar metabolism and fatty acid biosynthesis (the ACCases BC and BCCP, KAS II, and GPDHs involved in TAG synthesis), thereby promoting lipid accumulation under the addition of 0.2 M NaCl. However, high salinity inhibited cell growth. Expression of three SADs, whose encoded products function in unsaturated fatty acid biosynthesis, was up-regulated under high salinity (0.8 M NaCl addition). This research clarifies the relationship between salt tolerance and lipid accumulation and promotes the utilization of Chlorella sp. TLD6B.

Metabolomic Profiles of Shift Workers and Day Workers: A Cross-Sectional Study.

The purpose of this study was to characterize the metabolomic profiles of shift workers and day workers and to discover the effect of shift work on workers' metabolic health. A total of 824 participants aged 25 to 55 years were recruited, and 485 (275 shift workers and 210 day workers) completed the study. The mean age of the shift workers was 37.32 (5.53) years old, and that of day workers was 36.50 (7.83) years old. Serum and salivary samples were collected for the detection of key biochemical indicators (melatonin, cholesterol, and low-density lipoprotein cholesterol) and for metabolome profile analyses. Compared with female day workers, female shift workers had a higher BMI, waist circumference, and hip circumference. Correspondingly, we identified 76 significant metabolites (false discovery rate < 0.05) in shift workers, including L-tryptophan, acylcarnitines, and several fatty acids. Three pathways that presented significant differences were biosynthesis of unsaturated fatty acids, linoleic acid metabolism, and ubiquinone and other terpenoid-quinone biosynthesis. Compared with day workers, shift workers were more prone to weight gain and central obesity and were at a higher risk for impaired lipid metabolism with disrupted circadian rhythms.

Metatranscriptomic Analysis Reveals an Imbalance of Hepatopancreatic Flora of Chinese Mitten Crab Eriocheir sinensis with Hepatopancreatic Necrosis Disease.

Simple SummaryThe cause of Chinese mitten crab Eriocheir sinensis hepatopancreas necrosis disease (HPND) remains a mystery. In this study, metatranscriptomics sequencing was conducted to characterize the changes in the structure and gene expression of hepatopancreatic flora of crabs with and without typical symptoms of HPND; an imbalance of hepatopancreatic flora can be found in the crab with HPND, and the detected microbial taxa decreased, whereas the prevalence of Spiroplasma eriocheiris significantly increased in the hepatopancreatic flora of crabs with typical symptoms of HPND, and the relative abundances of the virus and microsporidia in crabs with HPND were very low and did not increase with disease progression. The differentially-expressed genes (DEGs) in hepatopancreatic flora between crabs with and without HPND were enriched ribosome, retinol metabolism, and biosynthesis of unsaturated fatty acid KEGG pathways. These results suggested that an imbalance of hepatopancreatic flora was associated with crab HPND, and the enriched pathways of DEGs were associated with the pathological mechanism of HPND.Hepatopancreas necrosis disease (HPND) of the Chinese mitten crab Eriocheir sinensis causes huge economic loss in China. However, the pathogenic factors and pathogenesis are still a matter of dissension. To search for potential pathogens, the hepatopancreatic flora of diseased crabs with mild symptoms, diseased crabs with severe symptoms, and crabs without visible symptoms were investigated using metatranscriptomics sequencing. The prevalence of Absidia glauca and Candidatus Synechococcus spongiarum decreased, whereas the prevalence of Spiroplasma eriocheiris increased in the hepatopancreatic flora of crabs with HPND. Homologous sequences of 34 viral species and 4 Microsporidian species were found in the crab hepatopancreas without any significant differences between crabs with and without HPND. Moreover, DEGs in the hepatopancreatic flora between crabs with severe symptoms and without visible symptoms were enriched in the ribosome, retinol metabolism, metabolism of xenobiotics by cytochrome P450, drug metabolism—cytochrome P450, biosynthesis of unsaturated fatty acids, and other glycan degradation. Moreover, the relative abundance of functions of DEDs in the hepatopancreatic flora changed with the pathogenesis process. These results suggested that imbalance of hepatopancreatic flora was associated with crab HPND. The identified DEGs were perhaps involved in the pathological mechanism of HPND; nonetheless, HPND did not occur due to virus or microsporidia infection.

Transcriptome analysis reveals the mechanism associated with dynamic changes in fatty acid and phytosterol content in foxtail millet (Setaria italica) during seed development

Foxtail millet (Setaria italica) is an excellent source of beneficial natural fatty acids and phytosterols. However, the mechanisms underlying the dynamic changes of fatty acids and phytosterols during seed development are unknown. In this study, a comprehensive dynamic change analysis of the bioactive compounds during seed development was conducted in two cultivars with different crude fat content (high-fat, JG 35 [5.40%]; and low-fat, JG 39 [2.90%]). GC-FID/MS analysis showed that the proportion of unsaturated fatty acids (UFAs) were higher than the saturated fatty acids (SFAs). UFA content first increased, then decreased during seed development, while SFA content showed the opposite trend. Oil contents continuously increased with seed development, especially at the S2 stage. Phytosterol contents initially increased, then decreased with seed development. Transcriptome analysis revealed that 152 genes were associated with fatty acid metabolism and phytosterol biosynthesis, of which 46 and 62 were related to UFA and phytosterol biosynthesis, respectively. Furthermore, the key genes involved in fatty acid synthesis (ACCase and FATA/B), triacylglycerol biosynthesis (LACS, GPAT, and DGAT), and phytosterols synthesis (CAS1, STM1, EGR6, and DWF1) were overexpressed. This led to maximum UFA, oil, and phytosterol accumulation in JG 35 at the S2 stage. This study reveals the mechanism behind the dynamic changes of fatty acid and phytosterol contents in foxtail millet during seed development.

An integrated approach to uncover quality markers of stir-baking Semen Cuscuta with salt solution preventing recurrent spontaneous abortion based on chemical and metabolomic profiling

The previous research of clinical big data mining showed that stir-baking Semen Cuscuta with salt solution (YP) ranked the first in the usage rate of treating abortion caused by kidney deficiency. At the same time, pharmacodynamic studies also showed that YP has better effect on improving recurrent spontaneous abortion (RSA) compared to raw products of Semen Cuscuta (SP). However, there were few studies on the biomarkers of YP improving RSA. In this study, the chemical and metabonomic profiling were used to screen the quality markers of YP on improving RSA. Firstly, a metabolomics study was carried out to select representative biomarkers of RSA. The ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UPLC-ESI-Q-TOF-MS) technique was used to investigate the components of exogenous and endogenous in serum of rats after administrated with YP and SP. As a result, 14 differential compounds were identified between the serum of rats administrated SP and YP. Compared to SP, there was an upward trend in YP of the compounds including kaempferol-3-glucuronide, iso-kaempferol-3-glucuronide, (1S) −11-hydroxyhexadecanoic acid and 3-phenylpropionic acid. Meanwhile, there was a reducing trend in YP of the compounds including kaempferol 3-arabinofuranoside, apigenin-3-O-glucoside, hyperoside, caffeic acid-β-D glucoside, dicaffeoylquinic acid, linoleic acid, 3,4-dicaffeoylquinic acid, caffeic acid, palmitic acid and methyl myristate. 12 biomarkers for RSA indication were identified. SP and YP have a certain effect on the endogenous biomarker. The regulation effect of YP was higher than that of SP. The main metabolic pathways included phenylalanine, tyrosine and tryptophan biosynthesis, glycerophospholipid metabolism, fatty acid biosynthesis, sphingolipid metabolism, biosynthesis of unsaturated fatty acids. This study demonstrated a promising way to elucidate the active chemical and endogenous material basis of TCM.

Short-chain fatty acids can improve lipid and glucose metabolism independently of the pig gut microbiota

BackgroundPrevious studies have shown that exogenous short-chain fatty acids (SCFAs) introduction attenuated the body fat deposition in conventional mice and pigs. However, limited studies have evaluated the effects of exogenously introduced SCFAs on the lipid and glucose metabolism independently of the gut microbiota. This study was to investigate the effects of exogenous introduction of SCFAs on the lipid and glucose metabolism in a germ-free (GF) pig model.MethodsTwelve hysterectomy-derived newborn pigs were reared in six sterile isolators. All pigs were hand-fed with sterile milk powder for 21 d, then the sterile feed was introduced to pigs for another 21 d. In the second 21-d period, six pigs were orally administrated with 25 mL/kg sterile saline per day and considered as the GF group, while the other six pigs were orally administrated with 25 mL/kg SCFAs mixture (acetic, propionic, and butyric acids, 45, 15, and 11 mmol/L, respectively) per day and regarded as FA group.ResultsOrally administrated with SCFAs tended to increase the adiponectin concentration in serum, enhance the CPT-1 activity in longissimus dorsi, and upregulate the ANGPTL4 mRNA expression level in colon (P < 0.10). Meanwhile, the mRNA abundances of ACC, FAS, and SREBP-1C in liver and CD36 in longissimus dorsi of the FA group were decreased (P < 0.05) compared with those in the GF group. Besides, the mRNA expression of PGC-1α in liver and LPL in longissimus dorsi tended to (P < 0.10) upregulate and downregulate respectively in the FA group. Moreover, oral administration of SCFAs tended to increase the protein level of GPR43 (P < 0.10) and decrease the protein level of ACC (P < 0.10) in liver. Also, oral administration of SCFAs upregulated the p-AMPK/AMPK ratio and the mRNA expressions of GLUT-2 and GYS2 in liver (P < 0.05). In addition, the metabolic pathway associated with the biosynthesis of unsaturated fatty acids was most significantly promoted (P < 0.05) by oral administration of SCFAs.ConclusionsExogenous introduction of SCFAs might attenuate the fat deposition and to some extent improve the glucose control in the pig model, which occurred independently of the gut microbiota.

Transferrin receptor 1 ablation in satellite cells impedes skeletal muscle regeneration through activation of ferroptosis.

BackgroundSatellite cells (SCs) are critical to skeletal muscle regeneration. Inactivation of SCs is linked to skeletal muscle loss. Transferrin receptor 1 (Tfr1) is associated with muscular dysfunction as muscle‐specific deletion of Tfr1 results in growth retardation, metabolic disorder, and lethality, shedding light on the importance of Tfr1 in muscle physiology. However, its physiological function regarding skeletal muscle ageing and regeneration remains unexplored.MethodsRNA sequencing is applied to skeletal muscles of different ages to identify Tfr1 associated to skeletal muscle ageing. Mice with conditional SC ablation of Tfr1 were generated. Between Tfr1 SC/WT and Tfr1 SC/KO (n = 6–8 mice per group), cardiotoxin was intramuscularly injected, and transverse abdominal muscle was dissected, weighted, and cryosectioned, followed by immunostaining, haematoxylin and eosin staining, and Masson staining. These phenotypical analyses were followed with functional analysis such as flow cytometry, tread mill, Prussian blue staining, and transmission electron microscopy to identify pathological pathways that contribute to regeneration defects.ResultsBy comparing gene expression between young (2 weeks old, n = 3) and aged (80 weeks old, n = 3) mice among four types of muscles, we identified that Tfr1 expression is declined in muscles of aged mice (~80% reduction, P < 0.005), so as to its protein level in SCs of aged mice. From in vivo and ex vivo experiments, Tfr1 deletion in SCs results in an irreversible depletion of SCs (~60% reduction, P < 0.005) and cell‐autonomous defect in SC proliferation and differentiation, leading to skeletal muscle regeneration impairment, followed by labile iron accumulation, lipogenesis, and decreased Gpx4 and Nrf2 protein levels leading to reactive oxygen species scavenger defects. These abnormal phenomena including iron accumulation, activation of unsaturated fatty acid biosynthesis, and lipid peroxidation are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis further exacerbates SC proliferation and skeletal muscle regeneration. Ferrostatin‐1, a ferroptosis inhibitor, could not rescue ferroptosis. However, intramuscular administration of lentivirus‐expressing Tfr1 could partially reduce labile iron accumulation, decrease lipogenesis, and promote skeletal muscle regeneration. Most importantly, declined Tfr1 but increased Slc39a14 protein level on cellular membrane contributes to labile iron accumulation in skeletal muscle of aged rodents (~80 weeks old), leading to activation of ferroptosis in aged skeletal muscle. This is inhibited by ferrostatin‐1 to improve running time (P = 0.0257) and distance (P = 0.0248).ConclusionsSatellite cell‐specific deletion of Tfr1 impairs skeletal muscle regeneration with activation of ferroptosis. This phenomenon is recapitulated in skeletal muscle of aged rodents and human sarcopenia. Our study provides mechanistic information for developing novel therapeutic strategies against muscular ageing and diseases.

Preliminary study on impacts of polystyrene microplastics on the hematological system and gene expression in bone marrow cells of mice

Microplastics (MPs) are currently a global environmental pollutants and health hazards that caused by MPs cannot be ignored. However, studies on MP toxicity in mammals are scare. Here, we investigated the effects of two doses (0.1 mg and 0.5 mg) of 5 µm polystyrene microplastic (PS-MP) particles on the hematological system of mice through traditional toxicology experiments and assessed the related potential biological mechanisms using transcriptome sequencing analysis. The toxicological examinations showed that the 0.5 mg dose significantly decreased white blood cell count, increased Pit count, and inhibited the growth of colony-forming unit CFU-G, CFU-M and CFU-GM. Compared with the control group, there were 41 differentially expressed genes (DEGs) in the 0.1 mg-treated group and 32 significantly changed genes in 0.5 mg-treated group. Of note, eight genes were found to be significantly altered in both the PS-MP-treated groups. Gene ontology analysis showed that DEGs were mainly involved in T cell homeostasis, response to osmotic stress, extracellular matrix and structure organization, and metabolic process of NADP and nucleotides. In addition, pathway analysis revealed that the Jak/Stat pathway, pentose and glucuronate interconversions, nicotinate and nicotinamide metabolism, biosynthesis of unsaturated fatty acids, and the pentose phosphate pathway were involved in PS-MP-induced toxicity in mice. These results indicated that PS-MP exposure can cause hematotoxicity to some extent, impact gene expression, and disturb related molecular and biological pathways in mouse bone marrow cells. Our study provides fundamental data on the hematotoxicity of PS-MPs in terrestrial mammals that will help to further assess the corresponding health risks in these mammals.