Search Results (466)

Diacylglycerol-O-acyltransferase 1 (DGAT1, EC 2.3.1.20) is a pivotal enzyme in plant triacylglycerol (TAG) biosynthesis. Previous work identified conserved di-arginine (R) motifs (R-R, R-X-R, and R-X-X-R) in its N-terminal cytoplasmic acyl-CoA binding domain. To elucidate their functional significance, we engineered R-rich sequences in the N-termini of Tropaeolum majus and Zea mays DGAT1s. Comparative analysis with their respective non-mutant constructs showed that deleting or substituting R with glycine in the N-terminal region of DGAT1 markedly reduced lipid accumulation in both Camelina sativa seeds and Saccharomyces cerevisiae cells. Immunofluorescence imaging revealed co-localization of non-mutant and R-substituted DGAT1 with lipid droplets (LDs). However, disruption of an N-terminal di-R motif destabilizes DGAT1, alters LD organization, and impairs recombinant oleosin retention on LDs. Further evidence suggests that the di-R motif mediates DGAT1 retrieval from LDs to the endoplasmic reticulum (ER), implicating its role in dynamic LD–ER protein trafficking. These findings establish the conserved di-R motifs as important regulators of DGAT1 function and LD dynamics, offering insights for the engineering of oil content in diverse biological systems. Full article

Abnormalities in plasma lipoproteins observed in patients with diabetes promote atherosclerosis. However, the association between various lipid species and classes and atherosclerosis remains unclear. Here, we aimed to identify the plasma lipid characteristics associated with atherosclerosis progression in patients with diabetes. We performed semi-targeted lipidomic analysis of fasting plasma samples using supercritical fluid chromatography coupled with mass spectrometry in two independent patient groups with type 2 diabetes (n = 223 and 31) and evaluated cross-sectional associations between plasma lipids and carotid intima-media thickness (CIMT). Ten plasma lipid species, including eight diacylglycerols (DGs), and total DG levels were significantly associated with CIMT in both groups. Patients of the former group were partly observed for 5 years, and we investigated associations between DGs and CIMT progression in these patients (n = 101). As a result, 22 DGs among the 26 identified DGs and total DG (β = 0.398, p < 0.001) were significantly associated with the annual change in CIMT. Furthermore, plasma DG levels improved the predictive ability for CIMT progression, with an adjusted R-squared increase of 0.105 [95% confidence interval: 0.010, 0.232] in the models. Plasma DGs are associated with CIMT progression in patients with type 2 diabetes. Measurement of total plasma DG levels may be beneficial in assessing the risk of atherosclerosis progression. Full article

Obesity and related metabolic disorders are closely linked to dysregulated lipid metabolism, where the metabolic balance of diacylglycerol (DAG) played a pivotal role. Although cis-palmitoleic acid (cPOA) exhibits anti-obesity effects, its efficacy varies across dietary conditions, and its molecular mechanisms remains unclear. In this study, we investigated the dose-dependent regulatory effects of cPOA on DAG metabolic shunting in db/db mice, employing lipidomics, pathway analysis, and gene/protein expression assays. Under a basal diet, low-dose cPOA (75 mg/kg) inhibited DAG-to-triglyceride (TAG) conversion, reducing hepatic lipid accumulation, while medium-to-high doses (150–300 mg/kg) redirected DAG flux toward phospholipid metabolism pathways (e.g., phosphatidylcholine [PC] and phosphatidylethanolamine [PE]), significantly lowering body weight and adiposity index. In high-fat diet (HFD)-fed mice, cPOA failed to reduce body weight but alleviated HFD-induced hepatic pathological damage by suppressing DAG-to-TAG conversion and remodeling phospholipid metabolism (e.g., inhibiting PE-to-PC conversion). Genetic and protein analyses revealed that cPOA downregulated lipogenic genes (SREBP-1c, SCD-1, FAS) and upregulated fatty acid β-oxidation enzymes (CPT1A, ACOX1), while dose-dependently modulating DGAT1, CHPT1, and PEMT expression to drive DAG metabolic shunting. Notably, DAG(36:3, 18:1–18:2) emerged as a potential biomarker for HFD-aggravated metabolic dysregulation. This study elucidated cPOA as a bidirectional regulator of lipid synthesis and oxidation, improving lipid homeostasis through dose-dependent DAG metabolic reprogramming. These findings provide novel insights and strategies for precision intervention in obesity and related metabolic diseases. Full article

Lard imparts unique organoleptic properties that underpin its essential role in Chinese gastronomy; however, the specific lipid precursors contributing to its aroma remain unclear. This study explores the flavor formation mechanism of lard by comparing its texture and aroma at two preparation temperatures, 130 °C and 100 °C. We identified a total of 256 and 253 lipids at these temperatures, respectively, with triacylglycerols (TGs) and diacylglycerols (DGs) being the predominant lipid species. An HS-GC-IMS analysis detected 67 volatile compounds, predominantly aldehydes, acids, and alcohols. A subsequent Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) identified 49 discriminatory lipids and 20 differential volatiles. A correlation analysis showed a positive relationship between aldehydes and unsaturated triglycerides in lard, with TG (16:1-16:1-18:0), TG (17:2-18:1-18:1), TG (16:1-17:1-18:1), and TG (18:1-18:1-20:1) identified as characteristic markers at both temperatures. Furthermore, there was a positive correlation between ketones and alcohols and phospholipids and sphingolipids containing unsaturated fatty acid chains. TGs and glycerophospholipids (GPs), rich in polyunsaturated fatty acids, are likely key precursors driving the formation of distinct flavors during lard processing. This study elucidates the mechanistic interactions between lipids and volatile organic compounds, providing a framework for optimizing lard processing protocols and flavor modulation. Full article

Mesenchymal stem cells (MSCs) exhibit low immunogenicity, multipotency, and are abundantly present in adipose tissue, making this tissue an easily accessible resource for regenerative medicine. Different commercial procedures have been developed to micro-fragment the adipose tissue aspirate from patients before its reinjection. We explored a commercial device which mechanically micro-fragments human lipoaspirate (LA) resulting in a homogeneous micro-fragmentation of fat tissue (MFAT). This device has been successfully employed in several clinical applications involving autologous adipose tissue transplantation. Here, we compare the untargeted/targeted lipidomic profile of LA and MFAT looking for differences in terms of qualitative modifications occurring during the handling of the original LA material. In MFAT, different lipid subclasses such as diacylglycerols, triacylglycerols, phospholipids, and sphingolipids are more represented than in LA. In addition, via targeted fatty acids analysis, we found a lower abundance of monounsaturated fatty acids in MFAT. The biological implications of these findings must be better investigated to contribute to a better understanding of the clinical efficacy of MFAT and for its potential use as a scaffold for drug delivery applications. Full article

We evaluated the effects of supplementing 1,3-diacylglycerol (1,3-DAG) in diets with different energy levels on the growth performance, nutrient digestibility, excreta scores, rectal temperature, meat quality, and blood parameters of broilers. A total of 576 one-day-old Ross 308 broilers (initial BW: 47.65 ± 0.51 g) were used in a 35-day feeding trial. The broilers were randomly assigned to four treatment groups (144 birds per group), with eight cages per group and 18 birds per cage, consisting of 9 males and 9 females. A 2 × 2 factorial design was employed, with two dietary energy levels (normal and reduced by 100 kcal/kg) with or without 0.075% 1,3-DAG supplementation. The results showed that compared with the diets without 1,3-DAG, the broilers receiving 1,3-DAG supplementation exhibited significantly greater body weight gain (BWG) and overall body weights (BWs) from days 10 to 35, along with a lower feed conversion ratio (FCR) (p < 0.05). In contrast, the low-energy diets without 1,3-DAG supplementation resulted in reduced growth performance, an increased FCR, higher drip loss, and lower total cholesterol levels. Notably, the rectal temperature and excreta scores were not affected by dietary energy levels or 1,3-DAG supplementation. In conclusion, while low-energy diets negatively impact growth and meat quality, 1,3-DAG supplementation enhances energy digestibility and growth performance, partially alleviating the adverse effects of reduced-energy diets and potentially lowering feed costs without compromising growth. Full article

Background/Objectives: Vitamin D (VD) is metabolized in the body and plays a crucial role in regulating the antioxidant system. While exposure to heavy metals (HMs) inhibits VD activity, HMs can also be absorbed following VD stimulation. Despite differing views on the interaction between HM and VD activity, the effects of HM exposure on VD-related pathways have not been examined using metabolomics. This study aimed to investigate the impact of HM exposure on VD-related antioxidant activity under VD deficiency conditions using untargeted metabolic profiling. Methods: In this retrospective cohort study, 46 plasma samples were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Metabolic profiling was performed on two groups: individuals with severe VD deficiency and low HM exposure (SVDD–LHM) and those with VD deficiency and high HM exposure (VDD–HHM). Results: As a compensatory response to oxidative stress induced by HMs, VD-related antioxidant pathways may be associated with elevated levels of antioxidants, including bilirubin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). In-creases in EPA and DHA were also linked to alterations in lipid metabolism, including diacylglycerol and phosphatidylcholine levels. DHA showed an area under the curve (AUC) of 0.850 (95% CI: 0.651–0.990), suggesting that DHA could serve as a potential biomarker for VD activity in response to HM exposure. Conclusions: The identified metabolites and metabolic pathways suggest that HM exposure may stimulate VD-related antioxidant activity, even under VD-deficient conditions. Full article

Background/Objectives: Abnormal brain glycerolipid metabolism has been reported for Alzheimer’s disease (AD). This includes both diacylglycerols (DGs) and monogalactosyl-DGs (MGDGs), which are elevated in AD subjects. While DGs are also elevated in subjects with mild cognitive impairment (MCI), MGDGs have not yet been examined at this early stage of cognitive impairment. Methods: MGDG, triacylglycerol (TG), and ether glycerolipid levels in the cerebral cortex gray matter of controls, MCI, and non-demented Alzheimer’s neuropathology (NDAN) subjects were monitored by high-resolution mass spectrometry (<2 ppm mass error). Results: MGDG, MGDG ether, DG ether, and TG levels were elevated in the cerebral cortex of MCI but not NDAN subjects. Conclusions: A diverse array of glycerolipids was elevated in MCI subjects, suggesting a role in cognitive dysfunction. This suggestion is further supported by the maintenance of normal glycerolipid levels in NDAN subjects with amyloid accumulation but not cognitive deficits. Our data clearly indicate that while complex lipid alterations occur in MCI subjects, relative to controls 20 years younger, no such lipid alterations occur in NDAN subjects. While amyloid deposition in MCI is not involved in the observed lipid alterations, other ongoing neuropathologies may contribute to changes in lipid dynamics and vice versa. Full article

Fatty acids (FAs) play a crucial role in human physiology, including energy production and serving as signaling molecules. However, a dysregulation in their balance can lead to multiple disorders, such as obesity and metabolic syndrome. These pathological conditions alter the balance between the heart’s energetic substrates, promoting an increased reliance on FAs and decreased cardiac efficiency. A therapeutic application of a non-psychotropic phytocannabinoid, cannabigerol (CBG), seems to be a promising target since it interacts with different receptors and ion channels, including cannabinoid receptors—CB₁ and CB₂, α2 adrenoceptor, or 5-hydroxytryptamine receptor. Therefore, in the current study, we evaluated a concentration-dependent effect of CBG (2.5 µM, 5 µM, and 10 µM) on H9c2 cardiomyocytes in lipid overload conditions. Gas–liquid chromatography and Western blotting techniques were used to determine the cellular lipid content and the level of selected proteins involved in FA metabolism, glucose transport, and the insulin signaling pathway. The glucose uptake assay was performed using a colorimetric method. Eighteen-hour CBG treatment in the highest concentration (10 µM) significantly diminished the accumulation of diacylglycerols (DAGs) and the saturation status of this lipid fraction. Moreover, the same concentration of CBG markedly decreased the level of FA transporters, namely fatty acid translocase (CD36) and plasma membrane fatty acid-binding protein (FABPpm), in the presence of palmitate (PA) in the culture medium. The results of our experiment suggest that CBG can significantly modulate lipid storage and composition in cardiomyocytes, thereby protecting against lipid-induced cellular dysfunction. Full article

Mammalian fertilization is triggered by a series of calcium (Ca²⁺) oscillations that are essential for egg activation and successful embryo development. It is widely accepted that Phospholipase C zeta (PLCζ) is the sperm-derived factor that triggers these oscillations, initiating egg activation through the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), leading to Ca²⁺ release. Several studies have reported a number of PLCζ mutations associated with polyspermy, egg activation failure and early embryonic arrest. Herein, six infertility-linked PLCζ mutations (I120M, L246F, L277P, S350P, A384V and M578T) spanning different domains of PLCζ were selected for characterization through in vivo assessment of their Ca²⁺-oscillation-inducing activities and complementary in silico analysis. Our data revealed that five of the investigated PLCζ mutants exhibited reduced or complete loss of in vivo Ca²⁺-oscillation-inducing activity, with the exception of the L277P, which resulted in increased frequency and duration of Ca²⁺ oscillations. Molecular modeling of PLCζ mutants was consistent with the in vivo characterization, revealing that most mutations have a deleterious effect on the structural stability. For the first time, we provide evidence that a gain-of-function PLCζ mutation may be a cause of fertilization failure in humans. Our findings suggest that PLCζ enzymatic activity must operate within an optimal range to ensure successful egg activation and early embryonic development. Additionally, we demonstrate the essential role of all PLCζ domains in maintaining the Ca²⁺ oscillation-inducing activity in eggs and the importance of PLCζ functionality in human fertilization. Full article

The Phosphoinositide Specific-Phospholipase C (PI-PLC) family of enzymes plays a crucial role in various cellular processes by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] into inositol 1,4,5-trisphosphate (IP₃) and diacylglycerol (DAG), which are essential messengers mediating critical intracellular signaling pathways. Herein, we carry out a comprehensive analysis of the structure, function, regulation, and implications of the PI-PLC family enzymes in both physiological and pathological contexts. More specifically, we discuss the structural features of PI-PLCs, elucidating their conserved domains and catalytic mechanisms. Furthermore, we explore the multifaceted roles of PI-PLCs in signal transduction, cellular homeostasis, and membrane dynamics, whilst highlighting the intricate regulatory mechanisms governing their activity such as protein–protein interactions, post-translational modifications, and lipid modulation. Lastly, we assess the involvement of PI-PLCs in various diseases, such as cancer, neurological disorders, immune dysregulation, and male infertility, emphasizing their potential as therapeutic targets. Full article

The paraventricular nucleus of the hypothalamus (PVN) regulates, among others, the stress response, sexual behavior, and energy metabolism through its magnocellular and parvocellular neurosecretory cells. Within the PVN, ensemble coordination occurs through the many long-range synaptic afferents, whose activity in time relies on retrograde neuromodulation by, e.g., endocannabinoids. However, the nanoarchitecture of endocannabinoid signaling in the PVN, especially during neuronal development, remains undescribed. By using single-cell RNA sequencing, in situ hybridization, and immunohistochemistry during fetal and postnatal development in mice, we present a spatiotemporal map of both the 2-arachidonoylglycerol (2-AG) and anandamide (AEA) signaling cassettes, with a focus on receptors and metabolic enzymes, in both molecularly defined neurons and astrocytes. We find type 1 cannabinoid receptors (Cnr1), but neither Cnr2 nor Gpr55, expressed in neurons of the PVN. Dagla and Daglb, which encode the enzymes synthesizing 2-AG, were found in all neuronal subtypes of the PVN, with a developmental switch from Daglb to Dagla. Mgll, which encodes an enzyme degrading 2-AG, was only found sporadically. Napepld and Faah, encoding enzymes that synthesize and degrade AEA, respectively, were sparsely expressed in neurons throughout development. Notably, astrocytes expressed Mgll and both Dagl isoforms. In contrast, mRNA for any of the three major cannabinoid-receptor subtypes could not be detected. Immunohistochemistry validated mRNA expression and suggested that endocannabinoid signaling is configured to modulate the activity of afferent inputs, rather than local neurocircuits, in the PVN. Full article

A new class of spiro[1,2,4]triazolo[1,5-c]quinazoline derivatives is presented as promising modulators of diacylglycerol kinase α (DGK-α), a target implicated in cancer, neurological disorders, and immune dysfunction. Through structure-based computational design using the CB-Dock2 platform with human DGK-α (PDB ID: 6IIE), 40 novel compounds were systematically evaluated along with established inhibitors (ritanserin, R59022, R59949, BMS502, and (5Z,2E)-CU-3) across five distinct binding pockets. Several compounds demonstrated binding profiles at the level of or surpassing the reference compounds. The physicochemical analysis revealed balanced drug-like properties with favorable molecular weights (252–412 g/mol) and appropriate three-dimensionality. The toxicological assessment indicated reassuring safety profiles with predicted LD₅₀ values of 1000–2000 mg/kg and minimal hepatotoxicity, carcinogenicity, and mutagenicity potential. Notably, compound 33 (adamantyl-substituted) emerged as exceptionally promising, exhibiting strong binding affinity, moderate solubility, and selective CYP inhibition patterns that minimize drug–drug interaction risks. Detailed molecular interaction mapping identified critical binding determinants, including strategic hydrogen bonding with TRP151, GLU166, and ARG126. The multidimensional evaluation identified compounds 13, 18, 33, and 40 as particularly promising candidates that balance potent target engagement with favorable pharmaceutical profiles, establishing this scaffold as a valuable platform for developing next-generation therapeutics targeting DGK-α -mediated signaling pathways. Full article

Studies in multiple species have shown that phospholipid:diacylglycerol acyltransferase (PDAT) and oil bodies are important factors affecting plant oil accumulation. Although the PDAT gene family has been extensively studied in many plants, it has not yet been systematically analyzed in Brassica napus. In this study, we identified four PDAT family members in B. napus, which were divided into two subfamilies based on phylogenetic analysis. These members share conserved motifs and gene structures, with multiple cis-acting elements related to plant hormones and abiotic stress in their promoter regions. Transcriptome sequencing revealed that most BnaPDAT genes are highly expressed during the late stages of seed development, with expression differences under various abiotic stresses and in materials with varying oleic acid content. To further investigate the effects of the PDAT gene on seed oil content and fatty acid composition in Brassica napus, we constructed transgenic plants overexpressing BnaA02.PDAT1 under the control of the 35S promoter. The results showed that compared to wild type (WT), the thousand-seed weight of BnaA02.PDAT1 transgenic plants increased significantly by 12.95–14.76%. Additionally, the total oil content in transgenic seeds was 1.86–2.77% higher than that of WT. Furthermore, the fatty acid composition in the seeds was also altered. This study confirms the critical role of BnaPDAT genes in B. napus seed development and their impact on oil accumulation. Full article

In this review article I briefly describe lipid self-assembly, interfacial curvature, and lyotropic phase diagrams. I then go on to describe how the phase behaviour can be controlled, and the structure of lyotropic phases can be tuned, by various parameters such as temperature, hydrostatic pressure, or the addition of amphiphilic molecules such as fatty acids, diacylglycerols, and cholesterol. I then give a few illustrations of how such structures/phases may play roles in lipid-based biotechnologies, and in biomembrane systems. Full article