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ABSTRACT Objective Methods Results Conclusions We here investigated whether lactation during puerperium could help to reverse the diabetogenic effect of gestation and further explored the lipid profiling changes upon breastfeeding.Thirty‐five women diagnosed with GDM were recruited, and fasting plasma samples were collected at ~6 weeks postpartum. Maternal metabolic parameters were determined, and an untargeted lipidomic analysis was performed. The relationship between underlying lipidomic responses and lactation was explored.Improved glucose homeostasis and insulin sensitivity were observed in GDM women who adopted breastfeeding during the puerperium. Further lipidomics analysis revealed prominent correlations between lipid constitution changes and breastfeeding in women with GDM. A total of 766 lipid species were identified, 33 of which were found to be significantly altered in response to lactation. Significant associations between dysregulated lipids and maternal metabolic parameters were also shown. Subsequently, we identified a panel of three lipids that were strongly associated with breastfeeding, from which we constructed a predictive model with higher discriminating power.We generally revealed that lactation during puerperium appears to have favorable effects on diabetogenic risk factors for GDM women. We also discovered that lipidomic changes related to lactation could elucidate the mother's recovery from GDM pregnancy. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer has emerged as a significant global health concern due to its high incidence and mortality, limited effectiveness of early detection, suboptimal treatment outcomes, and poor prognosis. Metabolic reprogramming is a prominent feature of cancer, and fatty acid metabolism assumes a pivotal role in bridging glucose metabolism and lipid metabolism. Fatty acids play important roles in cellular structural composition, energy supply, signal transduction, and other lipid‐related processes. Changes in the levels of fatty acid metabolite may indicate the malignant transformation of gastrointestinal cells, which have an impact on the prognosis of patients and can be used as a marker to monitor the efficacy of anticancer therapy. Therefore, targeting key enzymes involved in fatty acid metabolism, either as monotherapy or in combination with other agents, is a promising strategy for anticancer treatment. This article reviews the potential mechanisms of fatty acid metabolism disorders in the occurrence and development of gastrointestinal tumors, and summarizes the related potential biomarkers and anticancer strategies. [ABSTRACT FROM AUTHOR]

Lipidomic analysis of human serum is essential to monitor the individual's health status. Herein, we develop a facile strategy for rapid characterization of phospholipids in human serum via indium tin oxide (ITO) coated glass slide solid phase extraction MALDI mass spectrometry (ITO‐SPE‐MALDI‐MS). Phospholipid species are retained on ITO slide via solid phase extraction owing to the unique property of the ITO material; the measurement of phospholipid species from 1 μl human serum within 2 min is achievable. A comparison of ITO‐SPE strategy with conventional extraction methods was further carried out using liquid chromatography‐mass spectrometry (LC‐MS) and ion‐mobility mass spectrometry (IM‐MS), resulting in a comparable enrichment performance for the phospholipid analysis. Furthermore, rapid lipidomic profiling of serum samples from human colorectal cancer patients and cell lines was demonstrated. Our results indicate that ITO‐SPE‐MALDI‐MS provides a higher throughput strategy for the analysis of phospholipid species in complex biological mixtures, showcasing its potential for applications in the analysis of clinical biofluids. [ABSTRACT FROM AUTHOR]

Mulberry leaf is a widely used protein feed and is often used as a strategy to reduce feed costs and improve meat quality in the livestock industry. However, to date, there is a lack of research on the improvement of meat quality using mulberry leaves, and the exact mechanisms are not yet known. The results showed that fermented mulberry leaves significantly reduced backfat content but had no significant effect on intramuscular fat (IMF). Lipidomic analysis showed that 98 and 303 differential lipid molecules (p < 0.05) were identified in adipose and muscle tissues, respectively, including triglycerides (TG), phosphatidylcholine, phosphatidylethanolamine, sphingolipids, and especially TG; therefore, we analysed the acyl carbon atom number of TG. The statistical results of acyl with different carbon atom numbers of TG in adipose tissue showed that the acyl group containing 13 carbon atoms (C13) in TG was significantly upregulated, whereas C15, C16, C17, and C23 were significantly downregulated, whereas in muscle tissue, the C12, C19, C23, C25, and C26 in TG were significantly downregulated. Acyl changes in TG were different for different numbers of carbon atoms in different tissues. We found that the correlations of C (14–18) in adipose tissue were higher, but in muscle tissue, the correlations of C (18–26) were higher. Through pathway enrichment analysis, we identified six and four metabolic pathways with the highest contributions of differential lipid metabolites in adipose and muscle tissues respectively. These findings suggest that fermented mulberry leaves improve meat quality mainly by inhibiting TG deposition by downregulating medium‐ and short‐chain fatty acids in backfat tissue and long‐chain fatty acids in muscle tissue. [ABSTRACT FROM AUTHOR]

Aims: To investigate clusters of adipose tissue dysfunction, that is, with adipose tissue insulin resistance (ADIPO‐IR) and large waist circumference (WC), identify a worse lipidomic profile characterised by a high proportion of lipids rich in saturated fatty acids (SFA). Materials and Methods: Hierarchical clustering based on WC and ADIPO‐IR (calculated as fasting plasma non‐esterified fatty acids times fasting plasma insulin, FFA×INS), was performed in 192 adults with overweight/obesity and type 2 diabetes (T2D) treated with metformin (HbA1c = 7.8%). Free fatty acid composition and lipidomic profile were measured by mass spectrometry (GC‐MS and LC‐MSQTOF). Indexes of fatty acid desaturation (stearoyl‐coA desaturase‐1 activity, SCD116 = palmitoleic acid/palmitic acid and SCD118 = oleic acid/stearic acid) and of insulin resistance (HOMA‐IR) were also calculated. Results: Three clusters were identified: CL1 (ADIPO‐IR = 4.9 ± 2.4 and WC = 96±7 cm, mean ± SD), CL2 (ADIPO‐IR = 6.5 ± 2.5 and WC = 114 ± 7 cm), and CL3 (ADIPO‐IR = 15.0 ± 4.7 and WC = 107 ± 8 cm). Insulin concentrations, ADIPO‐IR, and HOMA‐IR significantly increased from CL1 to CL3 (all p < 0.001), while fasting glucose concentrations, HbA1c, dietary lipids and caloric intake were similar. Moreover, CL3 showed significantly higher concentrations of monounsaturated free fatty acids, oleic and palmitoleic acids, triglycerides (TAG) rich in saturated FA and associated with de novo lipogenesis (i.e., TAG 46–50), higher SCD116, SCD118, ceramide (d18:0/18:0), and phosphatidylcholine aa(36:5) compared with CL1/CL2 (all p < 0.005). Conclusions: High ADIPO‐IR and large WC identify a worse lipid profile in T2D characterised by complex lipids rich in SFA, likely due to de novo synthesis given higher plasma monounsaturated FFA and increased desaturase activity indexes. Registration Number Trial: ID NCT00700856 https://clinicaltrials.gov. [ABSTRACT FROM AUTHOR]

SUMMARY: CCT is required to regulate interorganelle contact sites through kinesin‐1 dynamics, modulating peroxisome and mitochondria activity, and ultimately controlling lipid cell content and metabolism. Cell proteostasis includes gene transcription, protein translation, folding of de novo proteins, post‐translational modifications, secretion, degradation and recycling. By profiling the proteome of extracellular vesicles (EVs) from T cells, we have found the chaperonin complex CCT, involved in the correct folding of particular proteins. By limiting CCT cell‐content by siRNA, cells undergo altered lipid composition and metabolic rewiring towards a lipid‐dependent metabolism, with increased activity of peroxisomes and mitochondria. This is due to dysregulation of the dynamics of interorganelle contacts between lipid droplets, mitochondria, peroxisomes and the endolysosomal system. This process accelerates the biogenesis of multivesicular bodies leading to higher EV production through the dynamic regulation of microtubule‐based kinesin motors. These findings connect proteostasis with lipid metabolism through an unexpected role of CCT. [ABSTRACT FROM AUTHOR]

Background and purpose: Circulating metabolites have been implicated in stroke pathogenesis, but their genetic determinants are understudied. Using a Mendelian randomization approach, our aim was to provide evidence for the relationship of circulating metabolites and the risk of stroke and its subtypes. Methods: Genetic instruments of 102 circulating metabolites were obtained from a genome‐wide association study, including 24,925 European individuals. Stroke was extracted from the MEGASTROKE dataset (67,162 cases; 454,450 controls) and a lacunar stroke dataset (7338 cases; 254,798 controls). The magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury were evaluated by a genome‐wide association study of white matter hyperintensities (N = 18,381), fractional anisotropy (N = 17,663), mean diffusivity (N = 17,467) and brain microbleeds (N = 25,862). The inverse‐variance weighted method Mendelian randomization was used as the primary analytical method, and directional pleiotropy and heterogeneity were examined in sensitivity analyses. Results: A genetic predisposition to a higher level of cholesterol in small and low‐density lipoprotein (LDL) was associated with risk of stroke (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.08–1.21, p = 5.98 × 10−7), especially for large‐artery atherosclerotic stroke (OR 1.34, 95% CI 1.19–1.52, p = 1.90 × 10−6). Total lipids in LDL particles were also associated with risk of stroke. A genetically determined higher cholesterol level in high‐density lipoprotein (HDL‐C) was associated with risk of intracerebral haemorrhage (OR 1.74, 95% CI 1.23–2.45, p = 1.66 × 10−3). No statistically significant association was found between genetic predisposition to circulating metabolites and magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury. Conclusions: Genetically determined levels of lipids in small LDL were associated with the risk of stroke, suggesting that a therapeutic strategy targeting small LDL levels may be crucial for stroke prevention. HDL‐C was positively associated with the risk of intracerebral haemorrhage. [ABSTRACT FROM AUTHOR]

Studies on the impact of ocean acidification on marine organisms involve exposing organisms to future acidification scenarios, which has limited relevance for coastal calcifiers living in a mosaic of habitats. Identification of tipping points beyond which detrimental effects are observed is a widely generalizable proxy of acidification susceptibility at the population level. This approach is limited to a handful of studies that focus on only a few macro‐physiological traits, thus overlooking the whole organism response. Here we develop a framework to analyze the broad macro‐physiological and molecular responses over a wide pH range in juvenile oyster. We identify low tipping points for physiological traits at pH 7.3–6.9 that coincide with a major reshuffling in membrane lipids and transcriptome. In contrast, a drop in pH affects shell parameters above tipping points, likely impacting animal fitness. These findings were made possible by the development of an innovative methodology to synthesize and identify the main patterns of variations in large ‐omic data sets, fitting them to pH and identifying molecular tipping points. We propose the broad application of our framework to the assessment of effects of global change on other organisms. [ABSTRACT FROM AUTHOR]

Nucleocytosolic transport, a membrane process, is impaired in motor neurons in amyotrophic lateral sclerosis (ALS). This study analyzes the nuclear lipidome in motor neurons in ALS and examines molecular pathways linked to the major lipid alterations. Nuclei were obtained from the frozen anterior horn of the lumbar spinal cord of ALS patients and age-matched controls. Lipidomic profiles of this subcellular fraction were obtained using liquid chromatography and mass spectrometry. We validated the mechanisms behind presumable lipidomic changes by exploring ALS surrogate models including human motor neurons (derived from ALS lines and controls) subjected to oxidative stress, the hSOD-G93A transgenic mice, and samples from an independent cohort of ALS patients. Among the differential lipid species, we noted 41 potential identities, mostly belonging to phospholipids (particularly ether phospholipids, as plasmalogens), as well as diacylglycerols and triacylglycerides. Decreased expression of alkyldihydroxyacetonephosphate synthase (AGPS)--a critical peroxisomal enzyme in plasmalogen synthesis--is found in motor neuron disease models; this occurs in parallel with an increase in the expression of sterol carrier protein 2 (SCP2) mRNA in ALS and Scp2 levels in G93A transgenic mice. Further, we identified diminished expression of diacylglycerol-related enzymes, such as phospholipase C ßI (PLCßI) and protein kinase CßII (PKCßII), linked to diacylglycerol metabolism. Finally, lipid droplets were recognized in the nuclei, supporting the identification of triacylglycerides as differential lipids. Our results point to the potentially pathogenic role of altered composition of nuclear membrane lipids and lipids in the nucleoplasm in the anterior horn of the spinal cord in ALS. Overall, these data support the usefulness of subcellular lipidomics applied to neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) dysfunction in aging and obesity has been related to chronic unresolved inflammation, which could be mediated by an impaired production of specialized proresolving lipid mediators (SPMs), such as Lipoxins-LXs, Resolvins-Rvs, Protectins-PDs, and Maresins-MaRs. Our aim was to characterize the changes in BAT SPMs signatures and their association with BAT dysfunction during aging, especially under obesogenic conditions, and their modulation by a docosahexaenoic acid (DHA)-rich diet. Lipidomic, functional, and molecular studies were performed in BAT of 2- and 18-month-old lean (CT) female mice and in 18-month-old diet-induced obese (DIO) mice fed with a high-fat diet (HFD), or a DHA-enriched HFD. Aging downregulated Prdm16 and UCP1 levels, especially in DIO mice, while DHA partially restored them. Arachidonic acid (AA)-derived LXs and DHA-derived MaRs and PDs were the most abundant SPMs in BAT of young CT mice. Interestingly, the sum of LXs and of PDs were significantly lower in aged DIO mice compared to young CT mice. Some of the SPMs most significantly reduced in obese-aged mice included LXB4, MaR2, 4S,14S-diHDHA, 10S,17S-diHDHA (a.k.a. PDX), and RvD6. In contrast, DHA increased DHA-derived SPMs, without modifying LXs. However, MicroPET studies showed that DHA was not able to counteract the impaired cold exposure response in BAT of obese-aged mice. Our data suggest that a defective SPMs production could underlie the decrease of BAT activity observed in obese-aged mice, and highlight the relevance to further characterize the physiological role and therapeutic potential of specific SPMs on BAT development and function. [ABSTRACT FROM AUTHOR]

Studies in mice with ablation of Prnp, the gene that encodes the cellular prion protein (PrPC), have led to the hypothesis that PrPC is important for peripheral nerve myelin maintenance. Here, we have used a nontransgenic animal model to put this idea to the test; namely, goats that, due to a naturally occurring nonsense mutation, lack PrPC. Teased nerve fiber preparation revealed a demyelinating pathology in goats without PrPC. Affected nerves were invaded by macrophages and T cells and displayed vacuolated fibers, shrunken axons, and onion bulbs. Peripheral nerve lipid composition was similar in young goats with or without PrPC, but markedly different between corresponding groups of adult goats, reflecting the progressive nature of the neuropathy. This is the first report of a subclinical demyelinating polyneuropathy caused by loss of PrPC function in a nontransgenic mammal. [ABSTRACT FROM AUTHOR]

Subclinical hypothyroidism is known to be associated with increased serum cholesterol. Since thyroid-stimulating hormone (TSH) exerts an inductor effect on cholesterol biosynthesis, we aimed to investigate the relationship between TSH mRNA and cholesterol metabolism in human adipose tissue (AT). Cross-sectionally, AT TSH-β (TSHB) mRNA was evaluated in 4 independent cohorts in association with serum total and LDL cholesterol, and AT lipidomics. Longitudinally, the effects of statins and of diet and exercise on AT TSHB mRNA were also examined. The bidirectional relationship between cholesterol and TSHB were studied in isolated human adipocytes. TSHB mRNA was consistently detected in AT from euthyroid subjects, and positively associated with serum total- and LDL-cholesterol, and with AT-specific cholesterol metabolism-associated lipids [arachidonoyl cholesteryl ester, C8-dihydroceramide, N-stearoyl-d-sphingosine, and GlcCer(18:0, 24:1)]. Reduction of cholesterol with statins and with diet and exercise interventions led to decreased TSHB mRNA in human AT, whereas excess cholesterol up-regulated TSHB mRNA in human adipocytes. In addition, recombinant human TSH α/β administration resulted in increased HMGCR mRNA levels in human adipocytes. In mice, subcutaneous AT Tshb expression levels correlated directly with circulating cholesterol levels. In summary, current results provide novel evidence of TSHB as a paracrine factor that is modulated in parallel with cholesterol metabolism in human AT. [ABSTRACT FROM AUTHOR]

Wild almond Amygdalus scoparia is a very fruitful tree that is spread over an extensive region of Iran. Considering its high quality oil, the development of clean extraction processes based on the use of compressed fluids is encouraged. In this study, the main factors involved in supercritical fluid extraction (SFE) and pressurized liquid extraction (PLE) of wild almond have been optimized by using two different experimental designs and considering the oil extraction yield as a response variable; effects of time, temperature, pressure, and use of co-solvents were studied for SFE while effects of time, temperature and type of solvent were evaluated for PLE. Results showed that the maximum oil yield using supercritical carbon dioxide was 42 %, obtained under the following conditions: extraction temperature, 40 °C; extraction pressure, 40 MPa; and 10 % ethanol as co-solvent. The optimum extraction yield for PLE was 55 %, which was achieved using ethanol as solvent at 150 °C for 20 min. Lipidomic analysis revealed that the amount of oleic acid in the oil extracted by SFE was higher than those obtained by using other classical procedures. In addition, triacylglycerols constituted more than 98 % of the extracted oils. [ABSTRACT FROM AUTHOR]

This paper describes a study of the phospholipid profile of Escherichia coli MG1655 cultures at the B and D periods of the cell cycle. The results indicate that the phosphatidyl glycerol fraction grows relatively rapidly and that the size of the cardiolipin (CL) fraction does not grow at all during cell elongation. This is consistent with observations that CL is located preferentially at the poles of E. coli . It also suggests that lipid production is controlled as a function of the cell cycle. [ABSTRACT FROM AUTHOR]

A simple gas chromatography-mass spectrometry (GC-MS) method has been developed for the determination of neutral lipids in yeast. This method was compared to the conventional thin-layer chromatography (TLC) method used in our laboratory. The new method enabled the measurement of molecular species of diacylglycerols, triacylglycerols, and sterol esters (SE). With a classic lipid extraction, samples can be injected directly into the GC-MS without any previous derivatization procedure. However, the main characteristic of this new method is its versatility because GC parameters can be modified based on the biological samples analyzed: volume and injection modes, derivatization of samples, etc. In order to validate the method, yeast lipid extracts from two distinct culture growth conditions were compared, the first in presence of oxygen and the second in its absence. Although the lipid profile of both yeast samples is qualitatively similar, the use of the GC-MS method rather than the TLC method enables the identification of a sterol, neoergosterol, in yeast cells grown in absence of oxygen. Moreover, this method enables phospholipid detection in samples but their identification is difficult. GC-MS total ion chromatogram of full chromatogram of yeast lipid extracts (positive values represent cells grown in the presence of oxygen while negative values represent cells grown without oxygen). STs: sterols; PLs: phospholipids; DAGs: diglycerides; SEs: sterol esters; TAGs: triglycerides. [ABSTRACT FROM AUTHOR]

The mdx mouse is a model for Duchenne muscular dystrophy (DMD), a debilitating disease affecting striated muscle. It is established that the fatty acid (FA) composition of skeletal muscle phospholipid (PL) is altered in mdx mice, but it is not known if cardiac muscle is similarly affected by dystrophin-deficiency. We tested FA profiles in PL and triacylglycerol (TAG) in cardiac muscle of 12-week old mdx and control (con) mice. Of 22 different FA, similar to our previous finding for skeletal muscle, the most abundant FA in heart PL were palmitic, stearic, cis-vaccenic, linoleic, and docosahexaenoic acid, while for TAG the most abundant FA were palmitic, oleic, cis-vaccenic, and linoleic acid. In comparing mdx and con, no significant group differences were detected for any FA in PL or TAG. Thus, unlike skeletal muscle, FA composition in cardiac muscle PL is not different between mdx and con at the age studied. The results can be understood in the context of tissue-specific disease severity in mdx mice, as pathology is quite modest in cardiac compared with skeletal muscle. [ABSTRACT FROM AUTHOR]