Triacylglycerol Levels Research Articles

Effect of different training modalities on lipid metabolism in patients with type ii diabetes mellitus: a network meta-analysis.

This study to evaluate the effects of different training modalities on blood lipids in type II diabetic patients by Network Meta-analysis, and provide a relevant basis for patients to develop exercise prescriptions to regulate blood lipids. Randomized controlled trials (RCTs) were retrieved from Zhiwang, Wanfang, Wipu, PubMed, EBSCO, Cochrane Library, and Web of Science that were published from the establishment to February 2023. Relevant statistical analyses were performed using Stata 17.0 software and Revman 5.4. A total of 35 randomized controlled trials with 2771 patients with type II diabetes were finally included. The results of Network Meta-analysis showed that, compared with the control group, Chinese traditional fitness exercise (CTF), resistance training (RT), and aerobic training (AT) could reduce total cholesterol (TC) levels; CTF, RT, whole body vibration training (WBV), and AT could reduce triacylglycerol (TG) levels; CTF, WBV and AT could increase High-density lipoprotein cholesterol (HDL) levels; CTF, RT and AT could reduce Low-density lipoprotein cholesterol (LDL) levels. SUCRA probability ranking results showed that CTF was the most effective in reducing TC[SMD= -0.57, 95% CI (-0.83, -0.31), p < 0.001], TG[SMD= -0.24, 95% CI (-0.36, -0.12), p < 0.001], LDL[SMD= -0.52, 95% CI (-0.70, -0.35), p < 0.001]; RT was the most effective in increasing HDL[SMD = 0.14, 95% CI (0.03, 0.26), p < 0.05]. CTF is more effective in improving TC, TG and LDL levels, while RT is most effective in improving HDL levels.

The acyltransferase transmembrane protein 68 regulates breast cancer cell proliferation by modulating triacylglycerol metabolism.

Cellular carcinogenesis is often marked by the accumulation of lipid droplets (LDs) due to reprogrammed lipid metabolism. LDs are dynamic organelles that primarily store intracellular triacylglycerol (TAG) and cholesteryl esters (CEs). Transmembrane protein 68 (TMEM68), a potential modifier of human breast cancer risk and outcomes, functions as a diacylglycerol acyltransferase, synthesizing TAG. However, the specific roles of TMEM68 in breast cancer cells remain unclear. Gene expression profiling interactive analysis and survival analysis were conducted. TMEM68 was overexpressed or knockdown in breast cancer cells to assess its impact on cell proliferation, migration and invasion. Targeted quantitative lipidomic analysis and quantitative polymerase chain reaction were used to profile lipid alterations and examine gene expression related to lipid metabolism following changes in TMEM68 levels. TMEM68 gene was upregulated in breast cancer patients and higher TMEM68 levels were associated with poorer survival outcomes. Overexpression of TMEM68 increased breast cancer cell proliferation and invasion, whereas knockdown had minimal or no impact on reducing proliferation and invasion. Altering TMEM68 levels resulted in corresponding changes in TAG levels and cytoplasmic LDs, with overexpression increasing both and knockdown decreasing them. Lipidomic analysis revealed that TMEM68 regulated TAG levels and altered diacylglycerol content in breast cancer cells. Additionally, TMEM68 influenced the metabolism of glycerophospholipids, CEs and acylcarnitines. TMEM68 also modified the expression of key genes encoding enzymes related to neutral lipid metabolism, including TAG and CEs. TMEM68 is highly expressed in breast cancer and negatively correlated with survival. Its overexpression promotes breast cancer cell proliferation while knockdown has varied effects depending on TMEM68 levels. TMEM68 regulates intracellular TAG and LDs contents along with alterations in glycerophospholipids. These findings suggest that TMEM68 may drive breast cancer cells proliferation by modulating TAG and LD content.

The protective effect of higher serum triacylglycerol (51:4) levels against Parkinson's disease.

Emerging evidence has shown a strong correlation between serum triacylglycerol (TAG) levels, the inflammatory response, and Parkinson's disease (PD) onset. However, the causal relationship between TAG levels and PD has not been well-established. We aimed to investigate the relationship between serum TAG levels and risk of PD and explore the potential mediating role of circulating immune cells and inflammatory proteins. We utilised genotype data from the GeneRISK cohort, and summary data from genome wide association studies investigating PD, circulating immune cells, inflammatory proteins, and plasma lipidomes. Using Mendelian randomization (MR) and multivariate MR (MVMR) analysis, we further adjusted for phosphatidylcholine (17:0_18:1) and triacylglycerol (58:7). Our results suggested a robust causal link between higher serum TAG (51:4) levels and a decreased risk of PD, with one standard deviation genetically instrumented higher serum TAG (51:4) level leading to a 21 percent [95% CI, 0.66 - 0.96] reduction in the risk of PD (p = 0.015). Additionally, the results of the mediation analysis suggested a possible role for mediation through circulating immune cells (including IgD-CD38-B cells and resting CD4 regulatory T cells), but not circulating inflammatory proteins, in the causal relationship between the plasma lipidomes and PD. Our study confirms a causal relationship between higher serum TAG (51:4) levels and a lower risk of PD and clarifies a possible role for mediation through circulating immune cells, but not inflammatory proteins. These findings indicate that serum triacylglycerol (51:4) regulates immunity to effectively lower the risk of PD.

Determination of the Biochemical Compositions of Stored Expressed Human Breast Milk of Healthy Lactating Mothers

Aims: This study is aimed at determining the biochemical compositions and immunological components of expressed human breast milk (HBM) gotten from healthy lactating mothers stored under varying low temperatures. Place and Duration of Study: Department of Microbiology, University of Benin, Benin, Edo State; and Quick Diagnostic Centre, Umuahia, Abia State. It was a three (3) months study. Methodology: Sixty (60) samples of expressed HBM were collected from healthy lactating mothers (at varying ages) in Abia State, Nigeria. Employing basic biochemical analyses, the quantification of total protein, glucose, and triacylglycerol levels, in addition to the confirmation tests of vitamin, minerals, and immune cells etc, were carried out. Results: The findings of this study demonstrated that triacylglycerol levels were constantly higher than glucose and protein level and this clearly was manifested across the ages of the lactating mothers (15 - 25 years, 26 - 35 years, and 36 - 45 years). Under room temperature and varying refrigeration, the changes in the biochemical compositions in the expressed HBM were also evaluated. Conclusion: From our findings, expressed HBM shows good nutritive profile with various bioactive factors that are essential for supporting infant growth, and immunity. Although references demonstrated that storage conditions can impact the nutritional value of expressed HBM, the result of this study was suggestive of expressed HBM having the ability to retain good amount of its bioactive compounds when refrigerated to 24 hours, ensuring that microbial infestations were properly controlled.

Differential Lipid Signatures of Lumbar and Cisternal Cerebrospinal Fluid

Background: The molecular composition of cerebrospinal fluid (CSF) is often used as a key indicator of biochemical alterations within distinct brain and spinal cord fluid compartments. The CSF protein content in lumbar CSF samples is widely employed as a biomarker matrix for diagnosing brain-related pathological conditions. CSF lipid profiles may serve as promising complementary diagnostics, but it remains unresolved if the lipid distribution is consistent along the neuroaxis. Methods: The lipid composition was determined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in cisternal CSF obtained from healthy subjects undergoing preventive surgery of an unruptured aneurism (n = 11) and lumbar CSF obtained from individuals referred for the clinical evaluation of cognitive dysfunction but subsequently cleared and deemed healthy (n = 19). Results: We reveal discernible variations in lipid composition along the neuroaxis, with a higher overall lipid concentration in cisternal CSF, although with different relative distributions of the various lipid classes in the two compartments. The cisternal CSF contained elevated levels of most lipid classes, e.g., sphingomyelins, lysophosphatidylcholines, plasmenylphosphatidylcholines, phosphatidic acids, and triacylglycerols, whereas a few select lipids from the classes of fatty acids, phosphatidylcholines, amides and plasmenylphosphatidylethanolamines were, oppositely, elevated in the lumbar CSF pool. Conclusions: The distinct lipid distribution along the neuroaxis illustrates that the molecular constituents in these two CSF compartments are not uniform. These findings emphasize the necessity of establishing a lumbar lipid index for the accurate interpretation of the cranial CSF lipid profile.

Effect of Mesembryanthemum crystallinum and its derived D‐pinitol on HMG‐CoA reductase and tyloxapol‐induced hyperlipedemia

AbstractSeveral previous research indicate that treating Mesembryanthemum crystallinum may aid in reducing adipogenesis and triacylglycerol level and improving hyperglycemia and diabetes. Therefore, the present study was designed to evaluate the effectiveness of M. crystallinum extract (MCE) in combating obesity and lowering fat/lipid/cholesterol levels. The study aimed to investigate the molecular docking model targeting 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR) using MCE‐derived d‐pinitol or atorvastatin, an inhibitor of HMGCR. In this study, histological alterations in the liver of tyloxapol‐induced hyperlipidemia (TIH) model, hyperlipidemia‐related markers in serum, HMGCR activity, and cell viability in HepG2 cells were analyzed. Our findings revealed that tyloxapol treatment significantly led to increased hyperlipidemia‐related indicators and cardiovascular‐associated risk indices. However, MCE effectively mitigated tyloxapol‐induced hepatic fat accumulation and an increase in cholesterol levels. This was achieved through improvements in metabolic parameters, ultimately ameliorating TIH. These beneficial results suggest that MCE may be a strong potential for the treatment of hyperlipidemia‐related diseases.

Exploring the response of yellow lupine (Lupinus luteus L.) root to drought mediated by pathways related to phytohormones, lipid, and redox homeostasis.

Yellow lupine (Lupinus luteus L.) is a high-protein crop of considerable economic and ecological significance. It has the ability to fix atmospheric nitrogen in symbiosis with Rhizobium, enriching marginal soils with this essential nutrient and reducing the need for artificial fertilizers. Additionally, lupine produces seeds with a high protein content, making it valuable for animal feed production. However, drought negatively affects lupine development, its mutualistic relationship with bacteria, and overall yield. To understand how lupine responds to this stress, global transcriptome sequencing was conducted, along with in-depth biochemical, chromatography, and microscopy analyses of roots subjected to drought. The results presented here contribute to strategies aimed at mitigating the effects of water deficit on lupine growth and development. Based on RNA-seq, drought-specific genes were identified and annotated to biological pathways involved in phytohormone biosynthesis/signaling, lipid metabolism, and redox homeostasis. Our findings indicate that drought-induced disruption of redox balance characterized by the upregulation of reactive oxygen species (ROS) scavenging enzymes, coincided with the accumulation of lipid-metabolizing enzymes, such as phospholipase D (PLD) and lipoxygenase (LOX). This disruption also led to modifications in lipid homeostasis, including increased levels of triacylglycerols (TAG) and free fatty acids (FFA), along with a decrease in polar lipid content. Additionally, the stress response involved alterations in the transcriptional regulation of the linolenic acid metabolism network, resulting in changes in the composition of fatty acids containing 18 carbons. The first comprehensive global transcriptomic profiles of lupine roots, combined with the identification of key stress-responsive molecules, represent a significant advancement in understanding lupine's responses to abiotic stress. The increased expression of the Δ12DESATURASE gene and enhanced PLD activity lead to higher level of linoleic acid (18:2), which is subsequently oxidized by LOX, resulting in membrane damage and malondialdehyde (MDA) accumulation. Oxidative stress elevates the activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT), while the conversion of FFAs into TAGs provides protection against ROS. This research offers valuable molecular and biochemical candidates with significant potential to enhance drought tolerance . It enables innovative strategies in lupine breeding and crop improvement to address critical agricultural challenges.

Lipid Alterations in Chronic Nonspecific Low Back Pain in the Chinese Population: A Metabolomic and Lipidomic Study

Chronic nonspecific low back pain (cNLBP) accounts for approximately 90% of low back pain cases, affecting 65–80% of the population and significantly impacting life quality and productivity. This condition also leads to substantial financial burden. Although there have been advancements, a comprehensive understanding of the underlying etiology of cNLBP remains elusive, resulting in less than optimal treatment outcomes. This study aimed to examine the correlation between lipid variations and the development of cNLBP. The cohort consisted of 26 healthy volunteers (HV group) and 30 cNLBP patients, with an assessment of metabolites and lipid composition in both groups. Metabolomic results revealed significant alterations in lipid-associated metabolites between the HV and cNLBP groups. Subsequent lipid analysis revealed that monoacylglycerols (MAGs) increased approximately 1.2-fold (p = 0.016), diacylglycerols (DAGs) increased approximately 1.4-fold (p = 0.0003), and phosphatidylserine (PS) increased approximately 1.4-fold (p = 0.011). In contrast, triacylglycerol (TAG) decreased to about 0.7-fold (p = 0.035) in the cNLBP group compared to the HV group. The contrasting trends in MAG/DAG and TAG levels indicated that the imbalance between MAG/DAG and TAG may have an impact on the development of cNLBP. This study has provided new insights into the relationship between the progression of cNLBP and specific lipids, suggesting that these lipids could serve as therapeutic targets for cNLBP.

REGULATOR OF FATTY ACID SYNTHESIS proteins regulate de novo fatty acid synthesis by modulating hetACCase distribution.

In plants, heteromeric acetyl-CoA carboxylase (hetACCase) initiates de novo fatty acid synthesis (FAS) by generating malonyl-CoA in the first committed step of this process. hetACCase activity is precisely regulated to meet the cellular demand for acyl chains during the plant life cycle. In this study, we performed a systematic co-expression analysis of hetACCase and its regulators in Arabidopsis (Arabidopsis thaliana) to better understand the regulatory mechanism of hetACCase. Our analysis uncovered REGULATOR OF FATTY ACID SYNTHESIS 1 (RFS1), whose expression is positively correlated with that of other regulators of hetACCase. The RFS gene family encodes two plastid inner envelope membrane proteins with undiscovered roles. Further analysis revealed that RFS1 co-localizes and directly interacts with CARBOXYLTRANSFERASE INTERACTOR 1 (CTI1). CRISPR/Cas9-mediated knockouts of RFSs exhibit enhanced hetACCase activity, higher FAS rates, and increased fatty acid contents, with particularly marked accumulation of absolute triacylglycerol levels in leaves, similar to cti mutants. The mutations of rfs and cti alter the plastid membrane distribution pattern of α-carboxyltransferase, leading to reduced hetACCase activity on the membrane, which could potentially be the original mechanism through which RFSs restrain hetACCase activity. Thus, we reveal a unique regulatory module that regulates de novo FAS and a genetic locus that may contribute to breeding of improved oil crops.

High-coverage targeted lipidomics revealed novel profile of serum lipid dysregulation in adult growth hormone deficiency.

Patients with adult growth hormone deficiency (AGHD) are at increased risk of metabolic syndrome. Despite extensive research efforts in recent decades, the lipid metabolism pattern of AGHD has yet to be thoroughly characterized. In this study, we used lipidomics analysis of fasting serum samples from 30 AGHD patients due to intracranial germ cell tumors (iGCTs) and 30 age-, gender-, and body mass index (BMI)-matched healthy controls to investigate the serum lipidomic pattern of AGHD patients due to iGCTs. We meticulously quantified 534 serum lipids from 29 classes using high-coverage targeted lipidomics technology in conjunction with a robust bioinformatics pipeline. Our results revealed an AGHD-specific dynamic change in serum lipidomic profile, manifested by higher overall levels of many lipid subclasses, including triacylglycerols (TAGs), diacylglycerols (DAGs), phosphatidylglycerols, phosphatidylethanolamines (PE), phosphatidylcholines (PC), phosphatidylinositols, ceramides, and bis(monoacylglycerol)phosphates than in healthy controls, and a distinct lowering level in alkyl PE (PE-O) and alkyl PC (PC-O). AGHD individuals with non-alcoholic fatty liver disease showed specific changes in higher TAG and DAG subclass levels. Alterations in lipid profiles may contribute to metabolic dysregulation in AGHD patients. TAGs, PCs, and PE-fatty acids positively correlated with BMI, fasting insulin, insulin resistance index, and adverse lipid parameters. In contrast, ether-linked PE-O, PC-O, and LysoPE-O showed a negative correlation. This study has significantly expanded the current understanding of lipid dysregulation in AGHD patients due to iGCT. These findings can potentially guide future research and the development of monitoring and intervention strategies.

Leveraging ML for profiling lipidomic alterations in breast cancer tissues: a methodological perspective

In this study, a comprehensive methodology combining machine learning and statistical analysis was employed to investigate alterations in the metabolite profiles, including lipids, of breast cancer tissues and their subtypes. By integrating biological and machine learning feature selection techniques, along with univariate and multivariate analyses, a notable lipid signature was identified in breast cancer tissues. The results revealed elevated levels of saturated and monounsaturated phospholipids in breast cancer tissues, consistent with external validation findings. Additionally, lipidomics analysis in both the original and validation datasets indicated lower levels of most triacylglycerols compared to non-cancerous tissues, suggesting potential alterations in lipid storage and metabolism within cancer cells. Analysis of cancer subtypes revealed that levels of PC 30:0 were relatively reduced in HER2(−) samples that were ER(+) and PR(+) compared to those that were ER(−) and PR(−). Conversely, HER2(+) tumors, which were ER(−) and PR(−), exhibited increased concentrations of PC 30:0. This increase could potentially be linked to the role of Stearoyl-CoA-Desaturase 1 in breast cancer. Comprehensive metabolomic analyses of breast cancer can offer crucial insights into cancer development, aiding in early detection and treatment evaluation of this devastating disease.

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.

Molecular characterization of CeOLE6, a diverged SH oleosin gene, preferentially expressed in Cyperus esculentus tubers.

CeOLE6, a tuber-specific gene in tigernut, encodes a diverged SH oleosin that functions in oil accumulation via homo and heteromultimerization. Tigernut (Cyperus esculentus L.) is a rare example accumulating high levels of triacylglycerols (TAGs) in underground tubers; however, the mechanism underlying is poorly understood. Given essential roles of oleosins (OLEs) in oil accumulation, in this study, structural and functional analyses were conducted for CeOLE6, an oleosin gene preferentially expressed in tigernut tubers. Phylogenetic analysis revealed that CeOLE6 encodes a diverged oleosin in Clade SH, which also includes CeOLE4 and -5. Further synteny analysis and sequence comparison indicated that CeOLE6 is more likely to be a whole-genome duplication (WGD) repeat of CeOLE4, which underwent rapid evolution and deletion of the typical C-terminal insertion for SHs. Nevertheless, CeOLE6 retains the capacity of oligomerization and oil accumulation, because (i) CeOLE6 could not only interact with itself but also with CeOLE2 and -5, two tuber-dominant members belonging to Clades SL and SH, respectively, and (ii) overexpressing CeOLE6 in tobacco leaves could significantly enhance the TAG content. Though CeWRI1 exhibits a similar expression pattern as CeOLE6 during tuber development, both CeWRI1 and -3 could not activate the CeOLE6 promoter, implying that they are not transcription factors contributing tuber-specific activation of CeOLE6. These findings not only provide insights into CeOLE genes in tuber oil accumulation, but also lay a foundation for further genetic improvement in tigernut and other species.

Pancreatic inflammation induced by hypothyroidism in female rabbits is associated with cholesterol accumulation and a reduced expression of CYP51A1, FXRβ, and PPARβ/δ.

In women and animal models, hypothyroidism induces hypercholesterolemia, pancreatitis, and insulitis. We investigated whether lipids are involved in the effects of hypothyroidism in the pancreas. Control (n = 6) and hypothyroid (n = 6) adult female rabbits were used. We quantified serum and pancreatic triacylglycerol and total cholesterol levels, the oxidative and antioxidant status, and the expression of low-density lipoprotein cholesterol receptor (LDLR) in the pancreas. Inflammation of the pancreas was evaluated by infiltration of immune cells positive to CD163 and α-farnesoid receptor (FXRα). Other lipid players involved in both inflammation and insulin secretion of the pancreas, such as lanosterol 14-α-demethylase (CYP51A1), β-farnesoid receptor (FXRβ), 3β-hydroxysteroid dehydrogenase (3β-HSD), and peroxisome proliferator-activated receptor β (PPARβ/δ), were quantified. Groups were compared by t-Student or U-Mann-Whitney tests (p ≤ 0.05). Hypothyroidism induced hypercholesterolemia and a high cholesterol accumulation in the pancreas of female rabbits, without affecting oxidative or antioxidative status nor the expression of LDLR. The pancreas of hypothyroid females showed inflammation identified by a great infiltration of immune cells, macrophages CD163+, and loss of expression of FXRα+ in immune cells. Moreover, a reduced expression of CYP51A1, FXRβ, and PPARβ/δ, but not 3β-HSD, in the hypothyroid pancreas was found. Pancreatitis and insulitis promoted by hypothyroidism may be related to the accumulation of cholesterol, lanosterol actions, and the activation of PPARβ/δ. All inflammatory markers evaluated in this study are related to glucose regulation, suggesting the link between hypothyroidism and diabetes.

Combination of Metabolomics, Lipidomics, and Molecular Biology for the Investigation of the Metabolic Disturbance of Short-Term Administration of Emodin.

Emodin, a natural anthraquinone derivative, is an active ingredient in many Chinese traditional herbs. Interestingly, although it is generally considered to possess hepatoprotective activity, some studies have also reported that it has a certain degree of hepatotoxicity. Additionally, the underlying metabolic regulation of emodin remains uncertain. Therefore, we conducted a nontargeted metabolomic study based on UHPLC/Q-Orbitrap-MS and NMR. Data are available via ProteomeXchange with the identifier PXD055000. The results indicated a close association between the short-term administration of emodin and lipid metabolism. Moreover, a lipidomics investigation utilizing QTRAP 6500+ UHPLC-MS/MS was conducted, with a focus on determining the position of C═C double bonds in unsaturated lipids based on Paternò-Büchi (PB) reaction to discover the metabolic disturbance more precisely. Specifically, lipidomics revealed elevated levels of free fatty acids (FFA) alongside notable reductions in sphingomyelin (SM) and triacylglycerol (TAG) levels. Furthermore, the combination of PB reaction and molecular biology results indicated that short-term administration of emodin may lead to the accumulation of n-6 polyunsaturated fatty acids by up-regulating the expression of FASN, stearyl CoA desaturase 1 (SCD1), and cytosolic phospholipase A 2 (cPLA2). Simultaneously, up-regulation of cyclooxygenase-2 (Cox-2) expression was observed, potentially fostering the production of prostaglandin E2 (PGE2) and subsequent inflammation.

The evaluation of Starmerella magnoliae X3 as a biodiesel feedstock based on triacylglycerol (TAG) production, lipid productivity, and fatty acid profile under nitrogen limitation and acidic pH conditions.

The effects of four initial culture pH values (3, 4, 5, and 6) and nitrogen limitation on growth, TAG accumulation, lipid production, fatty acid profile, and estimated biodiesel quality of Starmerella magnoliae X3 were investigated. TAG and lipid levels were measured by Nile Red fluorescence and sulfo-phospho-vanilin (SPV) techniques, respectively. The results showed that a combination of nitrogen limitation and acidic pH significantly (p < 0.05) increased TAG accumulation, total lipid contents, and lipid productivity in Starmerella magnoliae X3 compared to the control group. Under nitrogen limitation, the highest TAG accumulation was achieved at initial pHs of 3 and 5 after 72h of cultivation, and the highest lipid productivity (0.306g L-1 d-1) was observed after 48h at pH 3; the major fatty acids at the four pH values were oleic acid (63.6%-64%), palmitoleic acid (11.3%-12.5%), stearic acid (9.7%-11.4%), and palmitic acid (9.4%-10%). In addition, both stresses were associated with lower iodine value and higher cetane number of the biodiesel compared to the control. These findings suggest that cultivation in a low-nitrogen medium at an initial pH of 3 or 5 holds promise in increasing TAG production in Starmerella magnoliae X3.

Glucagon-like peptide-1 analog, liraglutide, regulates Sertoli cell energy metabolism.

Liraglutide, an analog of the incretin hormone glucagon-like peptide 1 (GLP-1), is widely used for obesity and type 2 diabetes treatment. However, there is scarce information about its effects on testicular function. Within the testis, Sertoli cells (SCs) provide nutritional support for germ cells; they metabolize glucose to lactate, which is delivered to germ cells to be used as a preferred energy substrate. Besides, SCs use fatty acids (FAs) as an energy source and store them as triacylglycerols (TAGs) within lipid droplets (LDs), which serve as an important energy reserve. In the present study, 20-day-old rat SC cultures were used to assess whether liraglutide affects their metabolic functions related to nutritional support and lipid storage. The results show that liraglutide does not modify glucose consumption or lactate production. However, it increases TAG levels and LD content. These effects are accompanied by an increase in the mRNA levels of the fatty acid transporter FAT/CD36, glycerol-3-phosphate-acyltransferase 3, and perilipins 1 and 4. The participation of the cAMP/PKA signaling pathway was explored. We observed that H89 (a PKA inhibitor) decreases the LD upregulation elicited by liraglutide, and that dibutyryl cAMP increases LD content and the expression of related genes. In summary, liraglutide promotes lipid storage in SCs through the regulation of key regulatory genes involved in FA transport, TAG synthesis, and LD formation. Considering the importance of lipid storage in SC energetic homeostasis maintenance, we postulate that liraglutide might improve the overall energetic status of the seminiferous tubule.

A specific serum lipid signature characterizes patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls. Metabolic control and dietary information biochemical markers were obtained from patients with GSDIa. Patients with GSDIa showed higher total serum lysophosphatidylcholine (Fold Change, (FC) 2.2, P < 0.0001), acyl-acyl-phosphatidylcholine (FC 2.1, P < 0.0001), and ceramide (FC 2.4, P < 0.0001) levels and bile acid (FC 0.7, P < 0.001), acylcarnitines (FC 0.7, P < 0.001), and cholesterol esters (FC 1.0, P < 0.001) than those of healthy controls, and higher di- (FC 1.1, P < 0.0001; FC 0.9, P < 0.01) and triacylglycerol (FC 6.3, P < 0.0001; FC 3.9, P < 0.01) levels than those of healthy controls and hypercholesterolemic subjects. Both total cholesterol and triglyceride values correlated with Cer (d16:1/22:0), Cer (d18:1/20:0), Cer (d18:1/20:0(OH)), Cer (d18:1/22:0), Cer (d18:1/23:0), Cer (d18:1/24:1), Cer (d18:2/22:0), Cer (d18:2/24:1). Total cholesterol also correlated with Cer (d18:1/24:0), Cer (d18:2/20:0), HexCer (d16:1/22:0), HexCer (d18:1/18:0), and Hex2Cer (d18:1/20:0). Triglyceridelevels correlated with Cer (d18:0/24:1). Alanine aminotransferase values correlated with Cer (d18:0/22:0), insulin with Cer (d18:1/22:1) and Cer (d18:1/24:1), and HDL with hexosylceramide (HexCer) (d18:2/23:0). These results expand on the currently known involvement of lipid metabolism in GSDIa. Circulating Cer may allow for refined dietary assessment compared with traditional biomarkers. Because specific lipid species are relatively easy to assess, they represent potential novel biomarkers of GSDIa.

Arabidopsis trigalactosyldiacylglycerol1 mutants reveal a critical role for phosphtidylcholine remodeling in lipid homeostasis.

Lipid remodeling plays a critical role in plant response to abiotic stress and metabolic perturbations. Key steps in this process involve modifications of phosphatidylcholine (PC) acyl chains mediated by lysophosphatidylcholine: acyl-CoA acyltransferases (LPCATs) and phosphatidylcholine: diacylglycerol cholinephosphotransferase (ROD1). To assess their importance in lipid homeostasis, we took advantage of the trigalactosyldiacylglycerol1 (tgd1) mutant that exhibits marked increases in fatty acid synthesis and fatty acid flux through PC due to a block in inter-organelle lipid trafficking. Here, we showed that the increased fatty acid synthesis in tgd1 is due to posttranslational activation of the plastidic acetyl-coenzyme A carboxylase. Genetic analysis showed that knockout of LPCAT1 and 2 resulted in a lethal phenotype in tgd1. In addition, plants homozygous for lpcat2 and heterozygous for lpcat1 in the tgd1 background showed reduced levels of PC and triacylglycerols (TAG) and alterations in their fatty acid profiles. We further showed that disruption of ROD1 in tgd1 resulted in changes in fatty acid composition of PC and TAG, decreased leaf TAG content and reduced seedling growth. Together, our results reveal a critical role of LPCATs and ROD1 in maintaining cellular lipid homeostasis under conditions, in which fatty acid production largely exceeds the cellular demand for membrane lipid synthesis.

Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice.

Microglia are critically involved in post-stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro-inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD-rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post-stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF-α, IL-6, and IL-1β as well as a pro-inflammatory phenotype and differentially expressed lipid metabolism-related genes. These post-ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post-ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury.