Fatty Acid Pathways Research Articles

Effects of Zinc Supplementation on Metabolomic Profiles in Tanzanian Infants: A Randomized Trial

BackgroundProvision of zinc supplementation to young children has been associated with reduced infectious morbidity and better growth outcomes. However, the metabolic pathways underlying these outcomes are unclear, and metabolomic data from humans undergoing zinc supplementation, particularly infants, are generally lacking. ObjectivesThis study aimed to examine the effect of zinc supplementation on metabolic profiles in Tanzanian infants aged 6 wk and 6 mo. MethodsBlood samples were collected at age 6 wk and 6 mo from 50 Tanzanian infants who were enrolled in a randomized placebo-controlled trial of zinc supplementation (5 mg oral daily). Metabolomic analysis using an ultrahigh-performance liquid chromatography/tandem mass spectroscopy platform was performed to identify potential metabolomic profiles and biomarkers associated with zinc supplementation. Principal component analysis (PCA) was used to summarize metabolomic data from all samples. Two-way repeated measures analysis of variance with compound symmetry covariance structures were used to compare metabolome levels over time between infants in the 2 treatment arms. ResultsIn PCA, the samples tended to be more separated by child age (6 wk compared with 6 mo) than by zinc supplementation status. We found that zinc supplementation affected a variety of metabolites associated with amino acid, lipid, nucleotide, and xenobiotic metabolism, including indoleacetate in the tryptophan metabolism pathway; 3-methoxytrosine and 4-hydrxoyphenylphruvate in the tyrosine pathway; eicosanedioate, 2-aminooctanoate, and N-acetyl-2-aminooctanoate in the fatty acid pathway; and N6-succinyladenosine in the purine metabolism pathway. Compared to the relatively small number of metabolites associated with zinc supplements, many infant metabolites changed significantly from age 6 wk to 6 mo. ConclusionsZinc supplementation, despite having overall clinical benefits, appears to induce limited metabolomic changes in blood metabolites in young infants. Future larger studies may be warranted to further examine metabolic pathways associated with zinc supplementation.The parent trial was registered at clinicaltrials.gov as NCT00421668.

Metabolic pathways associated with multi‐morbidity among Black caregivers of persons living with dementia

AbstractBackgroundBlack adults have the highest prevalence of obesity and hypertension, and these multiple chronic conditions increase their risk of morbidity and mortality. Black adults also represent the second largest group of caregivers of persons living with dementia. Gaps exist in our understanding of the physiologic changes associated with multiple chronic conditions in Black caregivers. This study used metabolomics to compare the metabolic profiles of Black caregivers with obesity, with or without hypertension. Our goal was to identify physiologic pathways for targeted interventions to improve morbidity/mortality in this group.MethodHigh‐resolution, untargeted metabolomics assays were run on stored serum samples from Black caregivers (n = 26) with obesity (BMI > = 30kg/m2), among whom 18 also had a diagnosis of hypertension. Linear regression using the xmsPANDA package was employed to identify metabolites differentiating multi‐morbidity. Two‐way hierarchical clustering analysis was used to visualize metabolome‐wide associations with multi‐morbidity. Additionally, metabolic pathways differentially impacted in multi‐morbidity were identified using mummichog.ResultOn average, caregivers were 62.9 (±6.5) years. 88.5% were female and 43% were married. Caregivers had been providing care for about 4.33 (±4) years. A total of 129 metabolites differentiated multi‐morbidity status at a p value < .05. Among these, key metabolic pathways associated with obesity and hypertension were butanoate metabolism and fatty acid activation. Among caregivers with only obesity, metabolites in the butanoate pathway were downregulated, compared to caregivers with both obesity and hypertension. Two exceptions were butyric acid and 2‐hydroxybutyric acid, which were both upregulated in caregivers without multi‐morbidity. In the fatty acid activation pathway, caregivers with only obesity had upregulated metabolites with the exception of icosatrienoic acid and dihomo‐gamma‐linolenic acid, which were down‐regulated.ConclusionIn caregivers with obesity, pathways associated with butanoate metabolism and fatty acid activation significantly differentiated hypertensive status. Healthcare interventions targeting caregiver education on diet/exercise may help optimize fatty acid activation in Black caregivers, thereby helping to reduce their risk of developing multi‐morbidities with hypertension. In addition, expanded health assessment of Black caregivers should be considered, as they may be at high risk for metabolic syndrome due to perturbed fatty acid and butanoate pathway functioning.

Abstract C084: Metabolomic profiling identifies molecular modifiers contributing to proteasome inhibitor resistance in multiple myeloma

Abstract Metabolic reprogramming plays a crucial role in the maintenance and differentiation of various cancers, including multiple myeloma (MM), the second-most common incurable hematological malignancy. Drug resistance poses a significant challenge to conventional proteasome inhibitor (PI) based therapy. A body of literature suggests that several metabolites are significantly deregulated in MM patients, however, their role in driving resistance is unclear. This study aims to identify metabolites modulated during acquired resistance to proteasome inhibitors in relapsed refractory (RR)MM. Two clinically relevant cell line models of PI-resistance (PIR) were developed by dose-escalation of the PI over one year. Cell cytotoxicity assays, immunoblotting, immunofluorescence, and flow cytometric analyses were used to assess the resistance phenotype. Mass spectrometry-based metabolomic profiling was performed to identify altered metabolites in resistant as compared to sensitive cell lines. PIR cells demonstrated pan-resistance to multiple PIs, including a >10-fold increase in IC50 for oprozomib compared to parental cells. PIR cells had higher bioenergetic and glycolytic activity (Seahorse) while gene expression profiling suggested downregulation of oxidative phosphorylation. Mass spectrometry-based metabolomic profiling identified distinct metabolites deregulated in drug-resistant cells. The metabolomic profiles of the drug-resistant cell lines showed that the lipid synthesis and beta-oxidation of fatty acid pathways were highly modulated. Several pathway components demonstrated a negative association with overall survival in multiple myeloma patient datasets (MMRF, GSE31161 & GSE9782). PI resistance led to increased phosphorylation of ACLY involved in fatty acid synthesis and increased expression of CPT1A indicative of activation of the beta-oxidation pathway. Use of ACLY and FASN tool compounds affected proliferation, survival, and response to treatment in PIR cells. Metabolites modulated during acquired resistance to proteasome inhibitor in relapsed refractory (RR)MM were identified and potential mechanisms driving resistance were studied. Citation Format: Snehal M Gaikwad, Vincent Keith Hughitt, Nana Gyabaah-Kessie, Mikaela Matera-Vatnick, Aleksandra A Michalowski, Anaisa Quintanilla-Arteaga, Thorkell Andresson, Beverly A Mock. Metabolomic profiling identifies molecular modifiers contributing to proteasome inhibitor resistance in multiple myeloma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C084.

오메가-6 대 오메가-3 비율의 기능의학적 의의

Omega-6 fatty acids and omega-3 fatty acids are essential fatty acids, which should be consumed and supplemented for the functioning of our bodies. The absolute essential fatty acids are linolenic acid and alpha-linolenic acid. However, considering the low conversion rate in vivo and their enzyme activity depending on individual genotype and disease condition, direct intake of gamma-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid is important. Requirements for essential fatty acids may vary from person to person. This means that the omega-6 and omega-3 fatty acid pathways compete to use the same enzymes, the modern Western diet focuses on omega-6 fats, and stress, aging, menopause, and relative deficiencies cause increased inflammation and decreased enzyme activity. The important thing is to consume or supplement fatty acids in a balanced manner rather than supplementing just one kind of 'healthy' fatty acid. Fatty acid imbalance is not a single problem but is complex and organically intertwined, so it usually causes complex problems. Excessive supplementation of one fatty acid can worsen the deficiency of other fatty acids, so wisdom is needed to supplement by checking blood omega-3 index and clinical evidence that can provide appropriate evidence.

Molecular insights into mutation-induced conformational changes in Acetyl CoA Carboxylase for improved activity

Acetyl-CoA carboxylase (ACCase) is crucial for fatty acid biosynthesis and has potential applications in lipid accumulation and advanced biofuel production. Mutations like S659A and S1157A in Saccharomyces cerevisiae ACCase remove the Snf1-regulation sites, resulting in increased enzyme activity with positive effects on the fatty acid pathway. However, the molecular-level understanding of these mutations on ACCase activity remains unexplored. Here, molecular dynamics simulation was conducted to investigate the mutations-induced conformational changes in S. cerevisiae ACCase. The wild-type ACCase was observed to have significant deviation in structure compared to mutant. Additionally, fluctuation of residues associated with biotin binding and Snf1-recognition were reduced in mutant compared to wild-type. Furthermore, the wild-type demonstrated opening motions of the domains, whereas the mutant showed closing movement. The mutation-induced conformational changes were analysed using network parameters, i.e., cliques/communities. The mutant showed an increase in sizes of several communities in AC3-AC4-AC5 domains leading to rigidification. Also, a new community was added in AC1-BT in the mutant, which suggested a substantial shift in the protein conformation. Thus, this study provides a theoretical understanding of the increased activity of ACCase due to two mutations, which can pave the path for enzyme engineering towards improved fatty acid-based fuel and chemical production.

α-Lipoic acid – a promising agent for attenuating inflammation and preventing steatohepatitis in rats fed a high-fat diet

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver disorder affecting a significant part of the global population. This study aimed to investigate the potential therapeutic effects of α-lipoic acid (α-LA) on the inflammatory response during simple steatosis development and progression into steatohepatitis. The study used the MASLD model in male Wistar rats that were fed a standard diet or a high-fat diet (HFD) for 8 weeks. Throughout the entire experiment, half of the animals received α-LA supplementation. The hepatic activity of pro-inflammatory n-6 and anti-inflammatory n-3 polyunsaturated fatty acid (PUFA) pathways and the concentration of arachidonic acid (AA) in selected lipid fractions were determined by the gas-liquid chromatography (GLC). The hepatic expression of proteins from inflammatory pathway was measured by the Western blot technique. The level of eicosanoids, cytokines and chemokines was assessed by the ELISA or multiplex assay kits. The results showed that α-LA supplementation attenuated the activity of n-6 PUFA pathway in FFA and DAG and increased the activity of n-3 PUFA pathway in PL, TAG and DAG. In addition, the administration of α-LA decreased the concentration of AA in DAG and FFA, indicating its potential protective effect on the deterioration of simple hepatic steatosis. The supplementation of α-LA also increased the expression of COX-1 and COX-2 with the lack of significant changes in prostaglandins profile. We observed an increase in the expression of 12/15-LOX, which was reflected in an increase in lipoxin A4 (LXA4) level. A decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines was also noticed in the liver of rats treated with HFD and α-LA. Our observations confirm that α-LA treatment has potential protective effects on inflammation development in the MASLD model. We believe that α-LA has a preventive impact when it comes to the progression of simple steatosis lesions to steatohepatitis.

Hydrothermal hydrogenation/deoxygenation of palmitic acid to alkanes over Ni/activated carbon catalyst

To produce paraffin from hydrogenation/deoxygenation of palmitic acid, model compound of bio-oil obtained by hydrothermal liquefaction (HTL) of microalgae, has been an attractive focus in recent years. In order to avoid energy-intensive separation process of water and bio-oil, it is of importance that deoxygenation upgrading of fatty acids under hydrothermal conditions similar with HTL process. Herein, it is the first time to explore the application of activated carbon (AC) supported non-noble-metal catalysts such as Ni, Co, and Mo, etc., in the hydrothermal hydrogenation/deoxygenation of long-chain fatty acids, and the obtained Ni/AC–H (the Ni/AC was further H2 pre-reduced) is one of the best catalysts. In addition, it is found that the catalytic activity can be further improved by H2 pre-reduction of catalyst. Characterization results that more low valences of nickel and oxygen vacancy can be obtained after H2 pre-reduction, thus significant promoting the deoxygenation especially the decarbonylation pathway of fatty acids. The total alkanes yield can reaches 95.9% at optimal condition (280 °C, 360 min). This work confirmed that the low-priced AC supported non-noble-metal catalysts have great potential compared with the noble-metal catalyst, in hydrothermal upgrading of bio-oil.

Nano-selenium foliar intervention-induced resistance of cucumber to Botrytis cinerea by activating jasmonic acid biosynthesis and regulating phenolic acid and cucurbitacin.

Botrytis cinerea is the primary disease affecting cucumber production. It can be managed by applying pesticides and cultivating disease-resistant cucumber strains. However, challenges, such as drug resistance in pathogenic bacteria and changes in physiological strains, are obstacles in the effective management of B. cinerea. Nano-selenium (Nano-Se) has potential in enhancing crop resistance to biological stress, but the exact mechanism for boosting disease resistance remains unclear. Here, we used metabolomics and transcriptomics to examine how Nano-Se, as an immune activator, induces plant resistance. Compared with the control group, the application of 10.0 mg/L Nano-Se on the cucumber plant's leaf surface resulted in increased levels of chlorophyll, catalase (10.2%), glutathione (326.6%), glutathione peroxidase (52.2%), cucurbitacin (41.40%), and metabolites associated with the phenylpropane synthesis pathway, as well as the total antioxidant capacity (21.3%). Additionally, the expression levels of jasmonic acid (14.8 times) and related synthetic genes, namely LOX (264.1%), LOX4 (224.1%), and AOC2 (309.2%), were up-regulated. A transcription analysis revealed that the CsaV3_4G002860 gene was up-regulated in the KEGG enrichment pathway in response to B. cinerea infection following the 10.0 mg/L Nano-Se treatment. In conclusion, the activation of the phenylpropane biosynthesis and branched-chain fatty acid pathways by Nano-Se promotes the accumulation of jasmonic acid and cucurbitacin in cucumber plants. This enhancement enables the plants to exhibit resistance against B. cinerea infections. Additionally, this study identified a potential candidate gene for cucumber resistance to B. cinerea induced by Nano-Se, thereby laying a theoretical foundation for further research in this area. © 2023 Society of Chemical Industry.

A Single-Nucleus Resolution Atlas of Transcriptome and Chromatin Accessibility for Peanut (Arachis Hypogaea L.) Leaves.

The peanut is an important worldwide cash-crop for edible oil and protein. However, the kinetic mechanisms that determine gene expression and chromatin accessibility during leaf development in peanut represented allotetraploid leguminous crops are poorly understood at single-cell resolution. Here, a single-nucleus atlas of peanut leaves is developed by simultaneously profiling the transcriptome and chromatin accessibility in the same individual-cell using fluorescence-activated sorted single-nuclei. In total, 5930 cells with 50890 expressed genes are classified into 18 cell-clusters, and 5315 chromatin fragments are enriched with 26083 target genes in the chromatin accessible landscape. The developmental trajectory analysis reveals the involvement of the ethylene-AP2 module in leaf cell differentiation, and cell-cycle analysis demonstrated that genome replication featured in distinct cell-types with circadian rhythms transcription factors (TFs). Furthermore, dual-omics illustrates that the fatty acid pathway modulates epidermal-guard cells differentiation and providescritical TFs interaction networks for understanding mesophyll development, and the cytokinin module (LHY/LOG) that regulates vascular growth. Additionally, an AT-hook protein AhAHL11 is identified that promotes leaf area expansion by modulating the auxin content increase. In summary, the simultaneous profiling of transcription and chromatin accessibility landscapes using snRNA/ATAC-seq provides novel biological insights into the dynamic processes of peanut leaf cell development at the cellular level.

The Genome of the Korean Island-Originated Perilla citriodora 'Jeju17' Sheds Light on Its Environmental Adaptation and Fatty Acid and Lipid Production Pathways.

Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla, Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.

Serum and follicular fluid metabolome and markers of ovarian stimulation.

What metabolic pathways and metabolites in the serum and follicular fluid are associated with peak estradiol levels and the number of mature oocytes? In the serum metabolome, mostly fatty acid and amino acid pathways were associated with estradiol levels and mature oocytes while in the follicular fluid metabolome, mostly lipid, vitamin, and hormone pathways were associated with peak estradiol levels and mature oocytes. Metabolomics has identified several metabolic pathways and metabolites associated with infertility but limited data are available for ovarian stimulation outcomes. A prospective cohort study of women undergoing IVF from 2009 to 2015. A total of 125 women undergoing a fresh IVF cycle at a fertility clinic in the Northeast United States who provided a serum and follicular fluid sample. Untargeted metabolomics profiling was conducted using liquid chromatography with high-resolution mass spectrometry in two chromatography columns (C18 and hydrophilic interaction chromatography (HILIC)). The main ovarian stimulation outcomes were peak serum estradiol levels and number of mature oocytes. We utilized adjusted generalized linear regression models to identify significant metabolic features. Models were adjusted for age,BMI, initial infertility diagnosis, and ovarian stimulation protocol. We then conducted pathway analysis using mummichog and metabolite annotation using level-1 evidence. In the serum metabolome, 480 and 850 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively. Additionally, 437 and 538 features were associated with mature oocytes in the C18 and HILIC columns, respectively. In the follicular fluid metabolome, 752 and 929 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively, Additionally, 993 and 986 features were associated with mature oocytes in the C18 and HILIC columns, respectively. The most common pathways associated with peak estradiol included fatty acids (serum and follicular fluid), hormone (follicular fluid), and lipid pathways (follicular fluid). The most common pathways associated with the number of mature oocytes retrieved included amino acids (serum), fatty acids (serum and follicular fluid), hormone (follicular fluid), and vitamin pathways(follicular fluid). The vitamin D3 pathway had the strongest association with both ovarian stimulation outcomes in the follicularfluid. Four and nine metabolites were identified using level-1 evidence (validated identification) in the serum and follicular fluid metabolomes, respectively. Our sample was majority White and highly educated and may not be generalizable to thewider population. Additionally, residual confounding is possible and the flushing medium used in the follicular fluid could have diluted our results. The pathways and metabolites identified by our study provide novel insights into the biologicalmechanisms in the serum and follicular fluid that may underlie follicular and oocyte development, which could potentially be used to improve ovarian stimulation outcomes. This work was supported by the following grants from the National Institute of Environmental Health Sciences (P30-ES019776, R01-ES009718, R01-ES022955, P30-ES000002, R00-ES026648, and T32-ES012870), and National Institute of Diabetes and Digestive and Kidney Diseases(P30DK046200). The authors have no competing interests to disclose. N/A.

Underlying Mechanisms for the Sex- and Chemical-Specific Hepatotoxicity of Perfluoroalkyl Phosphinic Acids in Common Carp (Cyprinus carpio).

The hepatotoxicities of perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been extensively investigated, while little is known about the sex-specific differences. In this study, common carp were exposed to the emerging perfluoroalkyl phosphinic acids (6:6 and 8:8 PFPiAs) for 14 days to disclose sex-specific hepatotoxicity. Apparent hepatotoxicity, including cell necrosis, apoptosis, and steatosis, was observed in both male and female carp liver. The observed hepatocyte steatosis was predominantly attributed to the dysregulation of hepatic lipid metabolism but was based on sex-specific mechanisms. It was manifested as inhibited oxidative decomposition of fatty acids (FAs) in the female liver, whereas it enhanced the uptake of FAs into the male liver, both of which led to excessive lipid accumulation. Untargeted lipidomics validated that the metabolism pathways of FA, sphingolipid, glycerolipid, and glycerophospholipid were disrupted by both compounds, leading to the generation of reactive oxygen species and oxidative stress. The oxidative stress further evolved into inflammation, manifested as promoted expression of proinflammatory cytokines and repressed expression of anti-inflammatory cytokines. Consistently, all of the changes were more noticeable in male carp, suggesting that male fish were more susceptible to PFPiA disruption. 8:8 PFPiA was less accumulated but caused stronger hepatotoxicity than 6:6 PFPiA, possibly because of the stronger binding capacity of 8:8 PFPiA to nuclear transcription factors mediating lipid metabolism and inflammation. The findings of this study highlight the significance of sex- and chemical-dependent bioaccumulation and the toxicity of PFASs in organisms.

Liver and Muscle Transcriptomes Differ in Mid-Lactation Cows Divergent in Feed Efficiency in the Presence or Absence of Supplemental Rumen-Protected Choline.

Improving dairy cow feed efficiency is critical to the sustainability and profitability of dairy production, yet the underlying mechanisms that contribute to individual cow variation in feed efficiency are not fully understood. The objectives of this study were to (1) identify genes and associated pathways that are altered in cows with high- or low-residual feed intake (RFI) using RNA sequencing, and (2) determine if rumen-protected choline supplementation during mid-lactation would influence performance or feed efficiency. Mid-lactation (134 ± 20 days in milk) multiparous Holstein cows were randomly assigned to either supplementation of 0 g/d supplementation (CTL; n = 32) or 30 g/d of a rumen-protected choline product (RPC; 13.2 g choline ion; n = 32; Balchem Corp., New Hampton, NY, USA). Residual feed intake was determined as dry matter intake regressed on milk energy output, days in milk, body weight change, metabolic body weight, and dietary treatment. The 12 cows with the highest RFI (low feed efficient; LE) and 12 cows with the lowest RFI (high feed efficient; HE), balanced by dietary treatment, were selected for blood, liver, and muscle analysis. No differences in production or feed efficiency were detected with RPC supplementation, although albumin was greater and arachidonic acid tended to be greater in RPC cows. Concentrations of β-hydroxybutyrate were greater in HE cows. Between HE and LE, 268 and 315 differentially expressed genes in liver and muscle tissue, respectively, were identified through RNA sequencing. Pathway analysis indicated differences in cell cycling, oxidative stress, and immunity in liver and differences in glucose and fatty acid pathways in muscle. The current work indicates that unique differences in liver and muscle post-absorptive nutrient metabolism contribute to sources of variation in feed efficiency and that differences in amino acid and fatty acid oxidation, cell cycling, and immune function should be further examined.

Metabolomics and transcriptomics based multi-omics integration reveals radiation-induced altered pathway networking and underlying mechanism

Recent advancement in integrated multi-omics has significantly contributed to many areas of the biomedical field. Radiation research has also grasped uprising omics technologies in biomarker identification to aid in triage management. Herein, we have used a combinatorial multi-omics approach based on transcriptomics together with metabolomics and lipidomics of blood from murine exposed to 1 Gy (LD) and 7.5 Gy (HD) of total-body irradiation (TBI) for a comprehensive understanding of biological processes through integrated pathways and networking. Both omics displayed demarcation of HD group from controls using multivariate analysis. Dysregulated amino acids, various PC, PE and carnitine were observed along with many dysregulated genes (Nos2, Hmgcs2, Oxct2a, etc.). Joint-Pathway Analysis and STITCH interaction showed radiation exposure resulted in changes in amino acid, carbohydrate, lipid, nucleotide, and fatty acid metabolism. Elicited immune response was also observed by Gene Ontology. BioPAN has predicted Elovl5, Elovl6 and Fads2 for fatty acid pathways, only in HD group. Collectively, the combined omics approach facilitated a better understanding of processes uncovering metabolic pathways. Presumably, this is the first in radiation metabolomics that utilized an integrated omics approach following TBI in mice. Our work showed that omics integration could be a valuable tool for better comprehending the mechanism as well as molecular interactions.

Predictable Representation of Metabolic Synthesis Pathways of Vitamins and Short-Chain Fatty Acids in Obese Adults

Predictable Representation of Metabolic Synthesis Pathways of Vitamins and Short-Chain Fatty Acids in Obese Adults

Rod-specific downregulation of omega-3 very-long-chain polyunsaturated fatty acid pathway in age-related macular degeneration

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, we compared omega-3 (n-3) fatty acid with DHA (22:6) and omega-6 (n-6) fatty acid with arachidonic acid (AA; 20:4) pathways. n-3 PC(22:6/22:6, 44:12) and n-6 PC(20:4/20:4, 40:8) showed differences among male/female, macula/periphery, and normal/AMD retinas. Periphery of AMD retina males increased 44:12 abundance, while normal females increased 40:8 (all macula had an upward 40:8 tendency). We also showed that female AMD switched from n-3 to n-6 fatty acids; most changes in AMD occurred in the periphery of female AMD retinas. DHA and VLC-PUFA release from PCs leads to conversion in pro-survival NPD1 and ELVs. The loss of the neuroprotective precursors of ELVs in the retina periphery from AMD facilitates uncompensated stress and cell loss. In AMD, the female retina loses peripheral rods VLC-PUFAs to about 33% less than in males limiting ELV formation and its protective bioactivity.

Microbial oil, alone or paired with β-glucans, can control hypercholesterolemia in a zebrafish model

Dyslipidemia is often associated with unhealthy dietary habits, and many mammalian studies have explored the mode of action of certain bioactive compounds such as β-glucans and n-3 PUFAs to understand their potential to normalize the lipid metabolism. There are only a few investigations that adopted omic approaches to unveil their combined effect on hypercholesterolemia. Zebrafish (Danio rerio) was used as a model organism to reveal the efficacy of Schizochytrium oil and β-glucans (from Euglena gracilis and Phaeodactylum tricornutum) against cholesterol-rich diet induced dyslipidemia. One of the folowing four diets was fed to a particular group of fish: a control high-cholesterol diet, a Schizochytrium oil diet or one of the two diets containing the oil and β-glucan. The plasma HDL, expression of hepatic genes linked to, among others, ferric ion binding and plasma phosphatidylcholines were higher and plasma cholesterol esters and triacylglycerols were lower in the microbial oil-fed fish compared to the fish fed high cholesterol diet. While the fish fed a mix of microbial oil and Euglena β-glucan had lower plasma triacylglycerols and expression of hepatic genes linked to PPAR signaling pathway and enriched biosynthesis of plasma unsaturated fatty acids, the fish fed microbial oil-Phaeodactylum β-glucan combination had lower abundance of triacylglycerols rich in saturated and mono-unsaturated fatty acids and cholesterol esters in the plasma.

DHA-Provoked Reduction in Adipogenesis and Glucose Uptake Could Be Mediated by Gps2 Upregulation in Immature 3T3-L1 Cells.

The signaling pathway of fatty acids in the context of obesity is an extensively explored topic, yet their primary mechanism of action remains incompletely understood. This study aims to examine the effect of docosahexaenoic acid (DHA) on some crucial aspects of adipogenesis in differentiating 3T3-L1 cells, using palmitic acid-treated (PA), standard differentiated, and undifferentiated adipocytes as controls. Employing 60 µM DHA or PA, 3T3-L1 preadipocytes were treated from the onset of adipogenesis, with negative and positive controls included. After eight days, we performed microscopic observations, cell viability assays, the determination of adiponectin concentration, intracellular lipid accumulation, and gene expression analysis. Our findings demonstrated that DHA inhibits adipogenesis, lipolysis, and glucose uptake by suppressing peroxisome proliferator-activated receptor gamma (Pparg) and G-protein coupled receptor 120 (Gpr120) gene expression. Cell cytotoxicity was ruled out as a causative factor, and β-oxidation involvement was suspected. These results challenge the conventional belief that omega-3 fatty acids, acting as Pparg and Gpr120 agonists, promote adipogenesis and enhance insulin-dependent glucose cell flux. Moreover, we propose a novel hypothesis suggesting the key role of the co-repressor G protein pathway suppressor 2 in mediating this process. Additional investigations are required to elucidate the molecular mechanisms driving DHA's anti-adipogenic effect and its broader health implications.

Genome-scale metabolic modeling and in silico analysis of opportunistic skin pathogen Cutibacterium acnes.

Cutibacterium acnes, one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The current limitations of acne treatment using antibiotics have caused an urgent need to develop a systematic strategy for selectively targeting C. acnes, which can be achieved by characterizing their cellular behaviors under various skin environments. To this end, we developed a genome-scale metabolic model (GEM) of virulent C. acnes, iCA843, based on the genome information of a relevant strain from ribotype 5 to comprehensively understand the pathogenic traits of C. acnes in the skin environment. We validated the model qualitatively by demonstrating its accuracy prediction of propionate and acetate production patterns, which were consistent with experimental observations. Additionally, we identified unique biosynthetic pathways for short-chain fatty acids in C. acnes compared to other GEMs of acne-inducing skin pathogens. By conducting constraint-based flux analysis under endogenous carbon sources in human skin, we discovered that the Wood-Werkman cycle is highly activated under acnes-associated skin condition for the regeneration of NAD, resulting in enhanced propionate production. Finally, we proposed potential anti-C. acnes targets by using the model-guided systematic framework based on gene essentiality analysis and protein sequence similarity search with abundant skin microbiome taxa.

Integrated multi-omics analysis reveals variation in intramuscular fat among muscle locations of Qinchuan cattle

BackgroundIntramuscular fat (IMF) is closely related to the tenderness, marbling, juiciness, and flavor of meat. We used a combined transcriptome and metabolome analysis to investigate the molecular mechanisms underlying phenotypic variation among Qinchuan cattle.ResultsThe IMF content was relatively high in the meat of Qinchuan cattle bulls and differed among muscle locations, namely the high rib (15.86%), ribeye (14%), striploin (10.44%), and tenderloin (8.67%). CCDC80 and the HOX gene cluster may regulate intramuscular adipose tissue deposition. Moreover, erucic acid (EA) was found to be the main metabolite in Qinchuan beef cattle, with a high concentration in IMF. The deposition of IMF could be regulated by the metabolic pathway for unsaturated fatty acids involving EA and the ACOX3, HACD2, and SCD5 genes. In addition, differentially expressed genes and metabolites were enriched in three major KEGG pathways: purine metabolism, pyrimidine metabolism, and the metabolism of glycine, serine, and threonine.ConclusionsWe identified a significant metabolite, EA, with variation in IMF. Its closely related genes, ACOX3, HACD2, and SCD5, co-regulate the metabolism of unsaturated fatty acids, ultimately affecting the accumulation of intramuscular adipose tissue in Qinchuan cattle. Consequently, Qinchuan cattle are an elite cultivar for high-quality beef production and have great potential for breeding.