Fatty Acids Research Articles

MOR23 deficiency exacerbates hepatic steatosis in mice.

Hepatic steatosis, a common liver disorder, can progress to severe conditions such as nonalcoholic steatohepatitis and cirrhosis. While olfactory receptors are primarily known for detecting odorants, emerging evidence suggests that they also influence liver lipid metabolism. This study generated a mouse model with a specific knockout of olfactory receptor 23 (MOR23) to investigate its role in hepatic steatosis. MOR23 knockout mice on a normal diet showed a slight increase in liver weight compared to wild-type (WT) mice. When fed a high-fat diet (HFD), these knockout mice exhibited accelerated hepatic steatosis, indicated by increased liver weight and hepatic triglyceride levels. Our findings suggest that the cyclic adenosine monophosphate/protein kinase A/AMP-activated protein kinase pathway is involved in the role of MOR23, leading to the upregulation of peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor-γ coactivator 1-α, and their target β-oxidation genes in the liver. MOR23 also appeared to regulate lipogenesis and free fatty acid uptake in HFD-fed mice, potentially by influencing sterol regulatory element-binding protein 1 activity. Notably, administering a potential MOR23 ligand, cedrene, attenuated hepatic steatosis in WT mice, but these effects were largely nullified in MOR23 knockout mice. These findings provide valuable insights into the invivo role of MOR23 in hepatic steatosis development.

Exploring Alkali Hydroxide Influence on Calcium Titanate Formation for Application in Biodiesel Catalysts

Biodiesel has been recognized as the most widely utilized biofuel around the world due to its significant role in reducing the consumption of crude oil and lowering environmental pollution levels. By serving as a renewable alternative to fossil fuels, bioethanol helps decrease greenhouse gas emissions and contributes to a more sustainable energy future. Traditionally, alkali hydroxides like NaOH and KOH have been mainstays in biodiesel synthesis. However, their overuse can lead to unwanted byproducts and operational complexities. Since calcium titanate can occur at a strong base condition, it presents an alternative avenue worth exploring. In this study, we investigate the influence of alkali hydroxides, namely LiOH, NaOH, and KOH, on the formation of calcium titanate through hydrothermal methods, with varying heating times. We aim to understand how different hydroxides affect the synthesis process and the resultant properties of calcium titanate. We delve into the vibrational properties of Ca‒O‒Ti and Ti‒O bonds using Fourier transform infrared spectroscopy (FTIR), confirming the presence of calcium titanate (JCPDS No.42-0423) through X-ray diffractometry (XRD). This thorough characterization provides insight into the structural integrity and composition of the synthesized materials. Moreover, scanning electron microscopy (SEM) reveals the intriguing cube-like morphology of calcium titanate, offering visual evidence of its unique structure. The fatty acid methyl ester Iimpressively, our results show that calcium titanate synthesized in 7 M NaOH and KOH solutions, heated for 24 hours, emerges as a promising biodiesel catalyst. We observe fatty acid methyl ester provides the percentages of 63.67% and 90.02%, respectively, indicating the catalytic efficacy of these materials in biodiesel production. These findings not only contribute to the understanding of calcium titanate synthesis but also pave the way for a sustainable future in biodiesel production by introducing efficient and eco-friendly catalysts.

Saturated Fats: Time to Assess Their Beneficial Role in a Healthful Diet

Saturated fats are widely seen as undesirable components of a healthy diet, as a result of their illusory association with elevated serum cholesterol. The regulation of serum cholesterol is now better understood and a lack of polyunsaturated fatty acids, rather than an abundance of saturated fatty acids, is responsible. Palmitic acid was shown to incite inflammation at unnaturally high concentrations in tissue culture, but later was found to play an auxiliary role as a precursor to ceramide biosynthesis and possibly in the palmitoylation of membrane receptors involved in the initiation of inflammation. Studies of arthritic inflammation in lab animals showed that dietary saturated fats are anti-inflammatory, whereas polyunsaturated oils are pro-inflammatory. Inflammation plays a role in numerous metabolic diseases, including insulin resistance, fatty liver disease and metabolic syndrome, among others. Fat, as triglycerides in adipose tissue, is an efficient way for living organisms to store energy and reduce the toxicity of other macronutrients. Macronutrients, such as excess carbohydrates and polyunsaturated fatty acids, are converted to saturated and monounsaturated fatty acids for storage as triglycerides in adipose tissue. Fatty acids are released from adipose tissue during fasting and as a result of some metabolic disorders, where elevated levels of nonesterified fatty acids in blood can lead to hepatic lipid accumulation, inflammation and insulin resistance. Although most serum nonesterified fatty acids may be saturated fatty acids, they are not necessarily derived from the diet. This paper will attempt to clarify the role of saturated fatty acids, and palmitic acid in particular, with regard to certain adverse health conditions.

Innovative Long-Acting Bisoprolol Patch: Synergistic Ion-Pair Skin Adsorption for Drug Delivery Control Coupled with Dynamic Modulation of Penetration Enhancers.

This study aims to develop a sustained release patch for bisoprolol (BSP) to address the issue of blood pressure fluctuations caused by traditional dosing methods, ensuring continuous drug release and efficient utilization. Long-chain saturated fatty acids (C6-C12) were chosen as counterions to precisely control BSP's permeation rate in the patch formulation, and the ion-pairing strategy's mechanism in drug delivery was thoroughly investigated. Molecular docking results revealed significant differences in the adsorption capacities of different ion pairs in the stratum corneum (SC) and epidermis, directly influencing their residence times and thereby regulating BSP's passive diffusion rate. Particularly, the BSP-C10 ion pair successfully reduced BSP's permeation rate to one-third of its baseline. To enhance drug delivery efficiency and reduce costs, chemical permeation enhancers (CPEs) are typically added to sustained release patches. In contrast to traditional static analyses based on cumulative permeation, this study utilized ATR-FTIR dynamic detection of isopropyl myristate (IPM) as a preferred enhancer, studying its disruptive effects on the skin barrier during drug delivery. The study observed that during drug delivery, the interaction between IPM and skin lipids follows a U-shaped trend: initially increasing, then decreasing, with the peak occurring at 10 h. Similarly, the drug delivery rate displays a comparable pattern. The addition of IPM as CPE increased the patch utilization rate from 39.8 ± 4.31 to 79.8 ± 7.27%. This strategy aims to rapidly reduce blood pressure in the initial phase with subsequent weakening of IPM disruption, allowing the ion-pairing strategy to dominate drug delivery control and maintain stable long-term therapeutic effects. Pharmacokinetic studies demonstrated that the newly developed BSP sustained release patch maintains stable blood drug concentrations, reduces burst release effects, increases bioavailability to 84.679%, doubles MRT0-t, halves Cmax, and significantly reduces the occurrence of blood pressure fluctuations.

The ability in managing reactive oxygen species affects Escherichia coli persistence to ampicillin after nutrient shifts.

This research delves into the intriguing realm of bacterial persistence and its profound implications for biofilms, infections, and antibiotic efficacy. The study focuses on Escherichia coli and how the switch from different carbon sources to fatty acids influences the formation of persister-resilient bacterial cells resistant to antibiotics. The findings reveal a striking variation in survival rates, with a significant number of cells surviving ampicillin treatment after transitioning from glucose to oleic acid. The key revelation is the role of reactive oxygen species (ROS) in cell killing, particularly after switching from gluconeogenic carbons. The timing of ROS bursts aligns with the rapid killing phase, highlighting the critical impact of oxidative stress regulation on persistence frequency. This research provides valuable insights into bacterial persistence mechanisms, offering potential avenues for targeted therapeutic interventions to combat bacterial resistance effectively.

Assessment of cardiac and skeletal muscle metabolites using 1H-MRS and chemical-shift encoded magnetic resonance imaging: Impact of diabetes, RAGE, and DIAPH1.

Diabetes affects metabolism and metabolite concentrations in multiple organs. Previous preclinical studies have shown that receptor for advanced glycation end products (RAGE, gene symbol Ager) and its cytoplasmic domain binding partner, Diaphanous-1 (DIAPH1), are key mediators of diabetic micro- and macro-vascular complications. In this study, we used 1H-Magnetic Resonance Spectroscopy (MRS) and chemical shift encoded (CSE) Magnetic Resonance Imaging (MRI) to investigate the metabolite and water-fat fraction in the heart and hind limb muscle in a murine model of type 1 diabetes (T1D) and to determine if the metabolite changes in the heart and hind limb are influenced by (a) deletion of Ager or Diaph1 and (b) pharmacological blockade of RAGE-DIAPH1 interaction in mice. Nine cohorts of male mice, with six mice per cohort, were used: wild type non-diabetic control mice (WT-NDM), WT-diabetic (WT-DM) mice, Ager knockout non-diabetic (RKO-NDM) and diabetic mice (RKO-DM), Diaph1 knockout non-diabetic (DKO-NDM), and diabetic mice (DKO-DM), WT-NDM mice treated with vehicle, WT-DM mice treated with vehicle, and WT-DM mice treated with RAGE229 (antagonist of RAGE-DIAPH1 interaction). A Point Resolved Spectroscopy (PRESS) sequence for 1H-MRS, and multi-echo gradient recalled echo (GRE) for CSE were employed. Triglycerides, and free fatty acids in the heart and hind limb obtained from MRS and MRI were compared to those measured using biochemical assays. Two-sided t-test, non-parametric Kruskal-Wallis Test, and one-way ANOVA were employed for statistical analysis. We report that the results were well-correlated with significant differences using MRI and biochemical assays between WT-NDM and WT-DM, as well as within the non-diabetic groups, and within the diabetic groups. Deletion of Ager or Diaph1, or treatment with RAGE229 attenuated diabetes-associated increases in triglycerides in the heart and hind limb in mice. These results suggest that the employment of 1H-MRS/MRI is a feasible non-invasive modality to monitor metabolic dysfunction in T1D and the metabolic consequences of interventions that block RAGE and DIAPH1.

Targeted metabolomics analysis of fatty acids in lamb meat for the authentication of paper mulberry silage as a substitute for alfalfa silage

Targeted metabolomics analysis of fatty acids in lamb meat for the authentication of paper mulberry silage as a substitute for alfalfa silage

Dry eye disease – how our lifestyle choices can affect the disease?

Introduction: In today’s world, we know how important it is to keep healthy habits because many diseases begin with daily lifestyle choices. Dry eye disease is a disease of the ocular surface and there are many risk factors, that lead to developing this disorder. As the possible factors we can underline deficiency of vitamin D or Omega-3 fatty acids, lack of physical exercise, long screen time, or smoking tobacco. Aim of the study: This review seeks to highlight the issue of dry eye disease linked to everyday routines by examining clinical trial outcomes. Furthermore, it offers an analysis of potential strategies to prevent ocular alterations by critically evaluating the existing data. State of knowledge: The listed lifestyle choices cause a higher risk of developing dry eye disease and affect ocular health on many levels, leading to unpleasant feelings and affecting people’s lives. However, with some lifestyle changes, the risk of developing this disease can be decreased, and negative symptoms can be minimized. It is important to remember vitamin D, and Omega-3 supplementation, daily physical activity, minimalization of the time spent in front of the visual display terminals, and quitting smoking. Conclusions: Many daily habits are connected to developing dry eye disease, and it is very important to remember about the small daily changes, which can decrease the risk of the disease.

Sustainable Abiotic-Biotic Dechlorination of Perchloroethene with Sulfidated Nanoscale Zero-Valent Iron as Electron Donor Source.

Combining organohalide-respiring bacteria with nanoscale zero-valent iron (nZVI) represents a promising approach for remediating chloroethene-contaminated aquifers. However, limited information is available regarding their synergistic dechlorinating ability for chloroethenes when nZVI is sulfidated (S-nZVI) under the organic electron donor-limited conditions typically found in deep aquifers. Herein, we developed a combined system utilizing a mixed culture containing Dehalococcoides (Dhc) and S-nZVI particles, which achieved sustainable dechlorination with repeated rounds of spiking with 110 μM perchloroethene (PCE). The relative abundance of Dhc considerably increased from 5.2 to 91.5% after five rounds of spiking with PCE, as evidenced by 16S rRNA gene amplicon sequencing. S-nZVI corrosion generated hydrogen as an electron donor for Dhc and other volatile fatty acid (VFA)-producing bacteria. Electron balance analysis indicated that 68.1% of electrons from Fe0 consumed in S-nZVI were involved in dechlorination, and 6.2, 1.1, and 3.2% were stored in formate, acetate, and other VFAs, respectively. The produced acetate possibly served as a carbon source for Dhc. Metagenomic analysis revealed that Desulfovibrio, Syntrophomonas, Clostridium, and Mesotoga were likely involved in VFA production. These findings provide valuable insights into the synergistic mechanisms of biotic and abiotic dechlorination, with important implications for sustainable remediation of electron donor-limited aquifers contaminated by chloroethenes.

MTORC1 and 2 adrenergic regulation and function in brown adipose tissue.

Brown adipose tissue (BAT) thermogenesis results from the uncoupling of mitochondrial inner membrane proton gradient mediated by the uncoupling protein 1 (UCP-1), which is activated by lipolysis-derived fatty acids. Norepinephrine (NE) secreted by sympathetic innervation not only activates BAT lipolysis and UCP-1, but uniquely in brown adipocytes, promotes "futile" metabolic cycles and enhances BAT thermogenic capacity by increasing UCP-1 content, mitochondrial biogenesis and brown adipocyte hyperplasia. NE exerts these actions by triggering signaling in the canonical G protein coupled b adrenergic receptors, cAMP and protein kinase A (PKA) pathway which, in brown adipocyte, is under a complex and intricated crosstalk with important growth-promoting signaling pathways such as those of mechanistic target of rapamycin (mTOR) complexes 1 (mTORC1) and 2 (mTORC2). This article reviews evidence suggesting that mTOR complexes are modulated by and participate in the thermogenic, metabolic, and growth-promoting effects elicited by NE in BAT and discusses current gaps and future directions in this field of research.

Multi-omics evaluation of clinical-grade human umbilical cord-derived mesenchymal stem cells in synergistic improvement of aging related disorders in a senescence-accelerated mouse model

BackgroundThe prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes.MethodsSAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites.ResultsHUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles.ConclusionThe administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases.

Seed Oil Contents, Fatty Acid Compositions, and Gossypol Concentrations of Some Okra Landraces

ABSTRACTOkra has recently attracted attention owing to its superior tolerance to high temperatures, greater adaptation to poor soil conditions, and having a robust plant structure. The plant contains a high amount of oil and valuable fatty acids; however, the main restriction of using okra seeds as an oil crop results from its gossypol contents. The aim of this study was to determine the oil content of okra landraces and to evaluate its potential as an oil crop. For this aim, seed oil content, fatty acid compositions of cold‐pressed seed oil, and gossypol concentrations of fruit, oil cake, and seed oil were investigated in a core collection of 26 okra landraces, lines, and cultivars. Individual plants were harvested at the full maturity stage, and seeds were harvested and dried under 35°C for 2 days prior to oil extraction. Oil content, fatty acid composition, and gossypol content were analyzed by NMR, GC‐FID, and HPLC, respectively. The calibration coefficients (r2) of all the methods were determined to be > 0.99. The seed oil content of the samples ranged between 12.15% and 18.83%. Linoleic (42.01%), palmitic (31.65%), oleic (18.39%), and stearic acids (3.20%) were found to be the largest fraction of the fatty acids. The data matrix from 19 fatty acids and oil content was subjected to Principle Component Analysis (PCA). As a result, 6 principal components (PCs, eigenvalues > 1) explained 83.84% of total variance in the data set, with PC1 contributing 32.69% of the total. Gossypol contents of the fruit, oil cake, and seed oil fractions ranged between LOQ‐2.12, < LOQ‐7.01, and < LOQ‐62.46 mg/kg, respectively. In conclusion, okra may have the potential to be an alternative oil crop for food/feed purposes due to the presence of reasonable oil content, high‐quality fatty acid variations, and very low amounts of toxic gossypols, warranting further breeding and agronomic studies.

Metabolome and Transcriptome Analyses Reveal Metabolomic Variations and Key Transcription Factors Involved in Lipid Biosynthesis During Seed Development in Carya illinoinensis

Plant oils are a large group of neutral lipids that play a vital role in the food and oleochemical industries. The pecan (Carya illinoinensis) is a promising woody oil crop known for its high-quality sources of essential fatty acids and various bioactive compounds that may aid in preventing heart diseases. However, there is still a lack of understanding regarding the accumulation of lipids and the molecular mechanism of lipid biosynthesis during seed development. This study aims to analyze the metabolite variations and molecular mechanisms of lipid biosynthesis by integrating untargeted metabolomics and transcriptomics during pecan seed development. A total of 293 differentially accumulated metabolites were identified and further categorized into 13 groups, with lipids and lipid-like molecules constituting the largest group. The oil content and fatty acid compositions of pecan embryos were assessed at three stages of seed development. Oleic acid (c18:1) and linoleic acid (c18:2n6) were found to be the most abundant unsaturated fatty acid components in pecan embryos. Additionally, a comprehensive analysis revealed 15,990 differentially expressed genes, with a focus on the key genes related to lipid metabolism. Furthermore, the study identified 1201 transcription factors from differentially expressed genes. These transcription factors were divided into 65 families, with different members in the same family exhibiting different expression patterns during seed development. The expression patterns of ten transcription factor genes during seed development were verified by qRT–PCR. Two key genes, CiABI3 and CiFUS3 were further cloned and found to be localized in the nucleus. This study used metabolome and transcriptome analysis during key periods of pecan seed development to identify the key genes associated with seed development and fatty acid biosynthesis.

Therapeutic Potential of Stearoyl-CoA Desaturase1 (SCD1) in Modulating the Effects of Fatty Acids on Osteoporosis

Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment.

Circulating metabolites in patients with chronic heart failure are related to increased lipid utilisation but not to gut microbiota alterations

Abstract Background The gut microbiota produces numerous metabolites that can enter the circulation and exert their effects outside the gut. Some have been implicated in the pathogenesis of chronic heart failure (HF). Several studies have reported altered gut microbiota composition and circulating metabolites in patients with chronic HF compared to healthy controls (HC). However, limited data is available on the potential interplay between the dysbiotic features of the gut microbiota and the altered circulating metabolome in these patients. Purpose To examine differences in circulating metabolites between patients with chronic HF and HC, and their association with cardiac function and gut dysbiosis. Methods We included 123 patients, aged 18-75 years, with stable chronic HF and left ventricular ejection fraction (LVEF) <40%, and 51 HC. We collected fasting blood samples for metabolomic and lipidomic analyses, which were performed using liquid chromatography tandem mass spectrometry. A web-based platform was utilised for data preprocessing, filtering, pathway analysis, and metabolite annotation. Principal component analysis and orthogonal partial least squares discriminant analysis were used to explore differences in plasma metabolic profiles. Over-representation analysis was performed to identify the pathways in which relevant metabolites were involved. Stool samples were sequenced using 16S ribosomal RNA gene amplification. We calculated a dysbiosis index for each sample based on different abundances of microbial taxa in patients vs. controls. Results After adjusting for age and sex, we identified 73 enriched metabolites and 27 enriched lipids (odds ratio≥2 and p<0.05), and 124 depleted metabolites and 6 depleted lipids (odds ratio≤0.5 and p<0.05) in HF patients compared to HC. The enriched metabolites were involved in pathways related to lipid metabolism (beta oxidation, glycerolipid, sex hormone, and fatty acid metabolism), pyrimidine metabolism, Warburg effect, citric acid cycle, and pentose phosphate pathway. The depleted metabolites were involved in pathways related to lipid biosynthesis (fatty acids, steroids, bile acids), amino acid metabolism (glycine, serine, taurine, hypotaurine, cysteine, selenoamino acids), polyamine biosynthesis (spermidine, spermine), sulphate/sulphite metabolism, propanoate and pyruvate metabolism, carbohydrate metabolism (galactose, amino sugars, glycolysis), transfer of acetyl groups into mitochondria, urea cycle, and beta oxidation of very long chain fatty acids (Figure 1). LVEF, N-terminal pro B-type natriuretic peptide, and the dysbiosis index were not significantly related to any metabolite. Conclusions In patients with chronic HF, energy metabolism is significantly altered compared to HC, with a notable shift towards lipid utilisation. However, the alterations in circulating metabolites were not related to markers of cardiac function and appear to be unrelated to gut dysbiosis.Figure 1

Lipidation Engineering in Daptomycin Biosynthesis.

Lipopeptides are an important family of natural products, some of which are clinically used as antibiotics to treat multidrug-resistant pathogens. Although the lipid moieties play a crucial role in balancing antibacterial activity and hemolytic toxicity, modifying the lipid moieties has been challenging due to the complexity of the lipidation process in lipopeptide biosynthesis. Here, we show that the lipid profile can be altered by engineering both secondary and primary metabolisms, using daptomycin as an example. First, swapping the fatty acyl AMP ligase (FAAL) gene dptF with foreign FAAL homologs improved the fatty acyl specificity of the lipidation process for decanoic acid. Then, the introduction of Mycobacterium type I fatty acid synthase operon (MvFAS-Ib/MvAcpS) and Cryptosporidium thioesterase (CpTEII) enriched the fatty acid pool with decanoic acid in Streptomyces roseosporus. The engineered fatty acid metabolism eliminates the need for external decanoic acid supplementation by enabling S. roseosporus to biosynthesize decanoic acid. By complete engineering of the lipidation process, we achieved, for the first time, high-purity, natural production of daptomycin. The lipidation engineering approach we demonstrate here lays the foundation for the lipidation control in lipopeptide biosynthesis.

Free fatty acids and mortality among adults in the United States: a report from US National Health and Nutrition Examination Survey (NHANES)

Abstract Introduction Free fatty acids (FFAs) serve as vital energy sources in multiple body tissues and they have been associated with elevated cardiovascular disease risk and mortality. There is a scarcity of prospective studies examining the associations between specific FFAs and long-term health outcomes. Purpose To examine the correlation between different FFAs types and all-cause or cardiovascular mortality in a large, nationally representative sample of adults in the United States (US), and examine how different concentrations and types of FFAs may mediate this association. Methods This cohort study included 3719 and 3900 participants in the unsaturated fatty acids (USFAs) and saturated fatty acids (SFAs) populations, respectively, who participated in the US National Health and Nutrition Examination Survey (NHANES) from 2011-2014. Multiple model calibration was performed using univariate and multivariate cox regression analysis to explore the associations between circulating FFAs and all-cause or cardiovascular mortality. Results The UFAs (myristoleic acid (14:1 n-5), palmitoleic acid (16:1 n-7), cis-vaccenic acid (18:1 n-7), nervonic acid (24:1 n-9), eicosatrienoic acid (20:3 n-9), docosatetraenoic acid (22:4 n-6), and docosapentaenoic acid (22:5 n-6)) were associated with an elevated risk of all-cause mortality ((hazard ratio (HR) 1.02 [1.006-1.034]; P=0.004), (HR 1.001 [1.001–1.002]; P＜ 0.001), (HR 1.006 [1.003–1.009]; P＜ 0.001), (HR 1.007 [1.002–1.012]; P = 0.003), (HR 1.027 [1.009–1.046]; P= 0.003), (HR 1.024 [1.012–1.036]; P＜ 0.001) and (HR 1.019 [1.006–1.032]; P = 0.005), respectively), whereas docosahexaenoic acid (22:6 n-3) was linked to a lower risk (HR 0.998 [0.996–0.999]; P = 0.007). Among SFAs, palmitic acid 16:0 was associated with a higher all-cause risk (HR 1.00 [1.00–1.00]; P = 0.022), while tricosanoic acid (23:0) and lignoceric acid (24:0) were associated with lower risks (HR 0.975 [0.959–0.991]; P = 0.002) and (HR 0.992 [0.984–0.999]; P = 0.036). Kaplan–Meier survival curves according to FFAs quartiles shown the highest risk for all-cause mortality was observed in the group with the highest concentration, except serum 23:0. The association between FFAs concentration and cardiovascular mortality in the multivariate analysis indicated that only 22:6 n-3 (HR 0.997 [0.994-1.000]; P=0.035) had a lower risk of cardiovascular mortality in the USFAs group, while none of the SFAs was found to be associated with cardiovascular mortality. While, the relationship between 22:6 n-3, and cardiovascular mortality was characterized by neither a linear nor nonlinear association (P-linear = 0.215; P-nonlinear = 0.260). Conclusion In this cohort of US adults, the types and concentrations of FFAs exhibited significant associations with risk of all-cause mortality. Achieving optimal concentrations of specific FFAs effectively lowered this risk of all-cause mortality, but this benefit was not observed in regards to cardiovascular mortality.FFA and all-cause mortality

Regulation of Rice Grain Weight by Fatty Acid Composition: Unveiling the Mechanistic Roles of OsLIN6 by OsARF12.

Fatty acids play a putative role as second messengers of phytohormones and regulate the rice grain weight. However, the inner mechanism is still unclear and needs to be further studied. In this study, we identified that oleic acid (C18:1) negatively correlates while linoleic acid (C18:2) positively correlates with rice grain weight. Field trials showed that 1000-grain weight was significantly reduced when treated with the fatty acid synthesis inhibitor, Firsocostat S enantiomer (FSE), at the heading and flowering stages. RNA-seq analysis revealed that FSE affects grain weight by modulating processes, such as glycolysis, sucrose metabolism, and hormone signaling. Notably, FSE inhibited the expression of OsLIN6, which is responsible for transporting C18:1 to the phosphatidylcholine pool for C18:2 synthesis. Compared with the wild type (WT), the OsLIN6 knockout mutant exhibited a lower grain weight, an increased C18:1 content, and a decreased C18:2 content. Importantly, OsARF12 was shown to bind to the OsLIN6 promoter and activate its expression. In summary, this study highlights the crucial role of the fatty acid synthesis gene, OsLIN6, which was regulated by OsARF12, in rice grain weight determination, thus establishing the molecular link between fatty acid synthesis and auxin signaling.

Lipin1 prevents ischemic heart disease by regulating lipid homeostasis

Abstract Background Lipid metabolism plays a crucial role in the pathophysiology of cardiovascular diseases. Lipin1 plays a pivotal role in lipid metabolism regulation. In the nucleus, Lipin1 acts as a transcriptional co-stimulatory molecule, interacting with peroxisome proliferator–activated receptor–gamma coactivator 1 alpha (PGC1α) and peroxisome proliferator–activated receptor alpha (PPARα). In the cytoplasm, Lipin1 functions as a phosphatidate phosphatase, converting phosphatidic acid to diacylglycerol to regulate lipid metabolism. Low expression of Lipin1 has been implicated in the severity of cardiac dysfunction in mice. Purpose This study aimed to investigate the role of Lipin1 in the cardiac remodeling after myocardial infarction (MI), revealing its impact on lipid metabolism and molecular pathway associated with cardiac dysfunction. Methods Two types of transgenic mice, cardiomyocyte-specific Lipin1 knockout (cKO) and overexpression (cOE) mice were used in this study. Eight to ten-week-old male mice were subjected to MI by coronary artery ligation. Cardiac lipid droplets were quantified, and triacylglycerol and free fatty acid levels were measured one week after MI surgery. Four weeks after MI, cardiac morphology and function were evaluated using echocardiography, alongside measurements of body weight (BW) and heart weight (HW). Additionally, gene expression analysis and histological evaluation were conducted to assess fatty acid metabolism, cardiac fibrosis, inflammation, and oxidative damage. Results Before MI surgery, there were no differences in HW/BW ratio, left ventricular end-diastolic diameter (LVDd) or LV fractional area change (LVFAC) among cKO/ cOE mice and their littermate controls. After MI, cKO mice exhibited significant cardiac dysfunction with larger LVDd, lower LVFAC and increased HW/BW ratio compared to littermate controls. This was accompanied by exacerbated cardiac fibrosis, increased inflammation, and augmented reactive oxygen species accumulation compared with their controls. Conversely, cOE mice displayed improved LVFAC, reduced cardiac fibrosis, inflammation, and reactive oxygen species accumulation compared to their littermate controls. Notably, the transgene of Lipin1 induced changes in the number of cardiac lipid droplets (LDs). cKO mice hearts showed a reduction in cardiac LDs with decreased levels of triacylglycerol and free fatty acids compared to the littermate controls. In contrast, cOE mice displayed increased cardiac LDs and upregulated expression of fatty acid metabolism–related genes after MI. Conclusion These results suggested that Lipin1 has a protective role against ischemic injury through controlling lipid metabolism in ischemic cardiomyocytes. Thus, Lipin1 emerges as a potential therapeutic target for myocardial infarction.

Taxonomic, Physiological, and Biochemical Characterization of Asterarcys quadricellularis AQYS21 as a Promising Sustainable Feedstock for Biofuels and ω-3 Fatty Acids

Asterarcys quadricellularis strain AQYS21, a green microalga isolated from the brackish waters near Manseong-ri Black Sand Beach in Korea, shows considerable potential as a source of bioactive compounds and biofuels. Therefore, this study analyzed the morphological, molecular, and biochemical characteristics of this strain; optimized its cultivation conditions; and evaluated its suitability for biodiesel production. Morphological analysis revealed characteristics typical of the Asterarcys genus: spherical to ellipsoidal cells with pyrenoid starch plates and mucilage-embedded coenobia. Additionally, features not previously reported in other A. quadricellularis strains were observed. These included young cells with meridional ribs and an asymmetric spindle-shaped form with one or two pointed ends. Molecular analysis using small-subunit rDNA and tufA sequences confirmed the identification of the strain AQYS21. This strain showed robust growth across a wide temperature range, with optimal conditions at 24 °C and 88 µmol m−2s−1 photon flux density. It was particularly rich in ω-3 α-linolenic acid and palmitic acid. Furthermore, its biodiesel properties indicated its suitability for biodiesel formulations. The biomass of this microalga may serve as a viable feedstock for biodiesel production and a valuable source of ω-3 fatty acids. These findings reveal new morphological characteristics of A. quadricellularis, enhancing our understanding of the species.