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Cardiac function is a dynamic process that must adjust efficiently to the immediate demands of physical state and activity. So too, the metabolic support of cardiac function is a dynamic process that must respond, in time, to the demands of cardiac function and viability. Flux through metabolic pathways provides chemical energy and generates signaling molecules that regulate activity among intracellular compartments to meet these demands. Thus, flux through metabolic pathways provides a dynamic mode of support of cardiomyocytes during physiological and pathophysiological challenges. Any inability of metabolic flux to keep pace with the demands of the cardiomyocyte results in progressive dysfunction that contributes to cardiac disease. Thus, the priority in maintaining and regulating flux through metabolic pathways in the cardiomyocyte cannot be understated. Great potential exists in current efforts to elucidate metabolic mechanisms as therapeutic targets for the diseased heart. As a consequence, detecting metabolic flux in the functioning myocardium of the heart, under normal and diseased conditions, is essential in elucidating the metabolic basis of contractile dysfunction. As a companion to the 2022 ISHR Research Achievement Award lecture, this review examines the use and applications of stable isotope kinetics to quantify metabolic flux through intermediary pathways and the exchange and transport of intermediates across the mitochondrial membrane and sarcolemma of intact functioning hearts in determining how these intracellular events are coordinated to support cardiac function and health. Finally, this work reviews recently demonstrated metabolic defects in diseased hearts and the potential for metabolic alleviation of heart disease. A glimpse inside cardiomyocyte metabolism within the beating heart via dynamic-mode 13C NMR spectroscopy reveals mechanisms coordinating pathophysiological state with metabolic flux. Delivery of carbon-13 (13C) enriched substates to the heart enable NMR-based detection (Middle panel showing sequential NMR spectra) of tricarboxylic acid (TCA) cycle and malate-aspartate (M/A) shuttle fluxes through progressive labeling of carbon positions within glutamate (GLU) (Top right panel, least squares fitting of metabolite pool content to enrichment at glutamate C-4 and C-3 carbons), as well as turnover of long chain fatty acids (LCFA) (blue squares) and initial exponential entry phase (red dotted line) within the triglyceride (TG) pool and (Bottom right panel) in the lipid droplets. End-point in vitro NMR of acetyl CoA enrichment and mass spectrometry of 13C and 12C enrichment of acyl groups in TG in sampled myocardium, enables measurement of total flux. Kinetic analysis of resulting isotopic enrichment curves coupled with end-point measures of metabolite pool size and 13C enrichment yield quantitative flux values in response to cardiac function and pathophysiological state. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Trisarcglaboids A and B were new family lindenane sesquiterpenoid trimer. • Compound 1 was highly cytotoxic to five human cancer cell lines. • Compound 1 potentially induced apoptosis by blocking Akt phosphorylation. Trisarcglaboids A and B (1 and 2), representing the first example of lindenane sesquiterpenoid trimers repolymerized based on the classical [4 + 2] type dimer, together with known biogenic precursors chlorahololide D (3) and sarcandrolide A (4), were identified as chemical components of the root of Sarcandra glabra. The novel trimeric lindenane sesquiterpenoid skeletons, including their absolute configurations, were characterized using MS, NMR, ECD, and X-ray single crystal diffraction. The proposed Diels-Alder cycloaddition between Δ 2(3) of the tiglic acyl group of the classical [4 + 2] type dimer and Δ 15(4),5(6) of the third lindenane may serve as the key biogenic step. In addition, compound 1 exerted significant cytotoxicity against five human cancer cell lines with IC 50 values ranging from 1 to 7 μM, potentially through blocking Akt phosphorylation and activating the endogenous apoptosis pathway. [ABSTRACT FROM AUTHOR]

Newborn screening (NBS) for metachromatic leukodystrophy (MLD) is based on first-tier measurement of sulfatides in dried blood spots (DBS) followed by second-tier measurement of arylsulfatase A in the same DBS. This approach is very precise with 0–1 false positives per ∼30,000 newborns tested. Recent data reported here shows that the sulfatide molecular species with an α-hydroxyl, 16‑carbon, mono-unsaturated fatty acyl group (16:1-OH-sulfatide) is superior to the original biomarker 16:0-sulfatide in reducing the number of first-tier false positives. This result is consistent across 4 MLD NBS centers. By measuring 16:1-OH-sulfatide alone or together with 16:0-sulfatide, the estimated false positive rate is 0.048% and is reduced essentially to zero with second-tier arylsulfatase A activity assay. The false negative rate is predicted to be extremely low based on the demonstration that 40 out of 40 newborn DBS from clinically-confirmed MLD patients are detected with these methods. The work shows that NBS for MLD is extremely precise and ready for deployment. Furthermore, it can be multiplexed with several other inborn errors of metabolism already tested in NBS centers worldwide. [ABSTRACT FROM AUTHOR]

Bighead carp head soup is a traditional Chinese cuisine with a pleasant aroma, but the effect of fish head phospholipids (FPLs) on the odorants is not fully understood. In this study, nuclear magnetic resonance (NMR), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and headspace solid-phase microextraction gas chromatography–mass spectrometry (HS-SPME–GC–MS) were used to monitor the oxidation products of phospholipids in fish head soup during the cooking process, and the fish head triglycerides (FTGs) were used as controls. In 1H NMR spectra, the signals of unsaturated acyl groups and the oxidation compounds in FPLs were significantly higher than those in FTGs. The results of FTIR showed that the changes of functional group absorptions of the oxidation compounds in FPLs were greater than FTGs. GC–MS demonstrated that FPLs samples produced more lipid-derived volatile compounds than FTGs samples. These results showed that FPLs were more prone to oxidation and could produce more lipid-derived odorants. Therefore, FPLs rather than FTGs, were the main precursor substance of lipid-derived odorants in bighead carp head soup. • NMR, ATR-FTIR and HS-SPME–GC–MS used to monitor phospholipid oxidation in fish head soup. • Unsaturated acyl groups and oxidation compounds in FPLs higher than those in FTGs. • FPLs samples produced more lipid-derived volatile compounds than FTGs samples. • FPLs were the main precursors of lipid-derived odorants in bighead carp head soup. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel HDACi were synthesized using a one-pot multi-component protocol as key step. • Compounds 8k and 8m were identified as highly selective HDAC6 inhibitors. • 8k and 8m showed significant inhibition of LPS-induced IL1B mRNA expression. Histone deacetylases (HDACs) are a class of enzymes that cleave acyl groups from lysine residues of histone and non-histone proteins. There are 18 human HDAC isoforms with different cellular targets and functions. Among them, HDAC6 was found to be overexpressed in different types of cancer. However, when used in monotherapy, HDAC6 inhibition by selective inhibitors fails to show pronounced anti-cancer effects. The HDAC6 enzyme also addresses non-histone proteins like α-tubulin and cortactin, making it important for cell migration and angiogenesis. Recently, the NLRP3 inflammasome was identified as an important regulator of inflammation and immune responses and, importantly, HDAC6 is critically involved the activation of the inflammasome. We herein report the design, synthesis and biological evaluation of a library of selective HDAC6 inhibitors. Starting from the previously published crystal structure of MAIP-032 in complex with CD2 of zHDAC6, we performed docking studies to evaluate additional possible interactions of the cap group with the L1-loop pocket. Based on the results we synthesized 13 novel HDAC6 inhibitors via the Groebke - Blackburn - Bienaymé three component reaction as the key step. Compounds 8k (HDAC1 IC 50 : 5.87 μM; HDAC6 IC 50 : 0.024 μM; selectivity factor (SF1/6): 245) and 8m (HDAC1 IC 50 : 3.07 μM; HDAC6 IC 50 : 0.026 μM; SF1/6: 118) emerged as the most potent and selective inhibitors of HDAC6 and outperformed the lead structure MAIP-032 (HDAC1 IC 50 : 2.20 μM; HDAC6 IC 50 : 0.058 μM; SF1/6: 38) both in terms of inhibitory potency and selectivity. Subsequent immunoblot analysis confirmed the high selectivity of 8k and 8m for HDAC6 in a cellular environment. While neither 8k and 8m nor the selectivity HDAC6 inhibitor tubastatin A showed antiproliferative effects in the U-87 MG glioblastoma cell line, compound 8m attenuated cell migration significantly in wound healing assays in U-87 MG cells. Moreover, in macrophages compounds 8k and 8m demonstrated significant inhibition of LPS-induced IL1B mRNA expression and TNF release. These findings suggest that our imidazo[1,2- a ]pyridine-capped HDAC6 inhibitors may serve as promising candidates for the development of drugs to effectively treat NLRP3 inflammasome-driven inflammatory diseases. [ABSTRACT FROM AUTHOR]

• Tannic acid (TA) and TiO 2 aqueous solution was used in interfacial polymerization. • TA coating on TiO 2 surface decreased the aggregations in top layer. • TA coating on TiO 2 surface improved inorganic/organic interfacial compatibility. • The obtained TFN membrane showed an excellent antibacterial property. • This study offered a new strategy to prepare high performance TFN NF membranes. A major issue hindering development of thin film nanocomposite (TFN) nanofiltration (NF) membrane is the interfacial defects induced by nanomaterial aggregation in top layer. Although various nanomaterials surface modification strategies have been developed to eliminate the interfacial defects, they usually involve extra modification steps and complex post-treatments. Inspired by the substrate-independent coating ability of tannic acid (TA) and the fact that the phenolic hydroxyl groups in TA can react with acyl chloride group in trimesoyl chloride, a TA coating solution containing TiO 2 nanoparticles was used as an aqueous phase of interfacial polymerization to prepare interfacial modified TFN NF membranes in this study. Surface modification of TiO 2 nanoparticles and interfacial polymerization can be carried out in a single step without any extra pre-modification step. It was found that the TA coating on TiO 2 nanoparticles surface could decrease TiO 2 aggregations and enhance interfacial compatibility between TiO 2 and polyester matrix. The TFN NF membrane prepared at a TiO 2 loading of 0.020 wt% exhibited a pure water flux of 28.8 L m-2 h−1 (284% higher than that of the controlled TFC membrane), and possessed enhanced NaCl and Na 2 SO 4 rejections of 57.9% and 94.6%, respectively, breaking through the trade-off between permeability and selectivity. [ABSTRACT FROM AUTHOR]

• U. hordei produced mono-acetylated MEL-C as a result of the specificity of UhMat1. • Incorporation of C 16 and C 4 fatty acids in UhMELs depends on enzyme specificities. • Mac1 is responsible for of the small fatty acids at the mannose position C2. • Mac2 adds the medium chain length fatty acids to the mannose residue C3. Mannosylerythritol lipids (MELs) are surface active molecules produced by many basidiomycetous fungi. MELs consist of a mannosylerythritol disaccharide, which is acylated with short and medium chain fatty acids at the mannosyl moiety. A gene cluster composed of five genes is required for MEL biosynthesis. Here we show that the plant pathogenic fungus Ustilago hordei secretes these glycolipids under nitrogen starvation conditions. In contrast to MELs produced by the closely related fungus Ustilago maydis those secreted by U. hordei are mostly mono-acetylated and contain a different mixture of acyl groups. Cross-species complementation between these fungi revealed that these differences result from different catalytic activities of the acetyltransferase Mat1 and the acyltransferases Mac1 and Mac2. U. maydis mat1 mutants expressing the homologous mat1 gene from U. hordei produced mostly mono-acetylated variants and lack di-acetylated MELs normally produced by U. maydis. Furthermore, we determined that the acyltransferase Mac1 acylates the mannosylerythritol moiety at position C2 while Mac2 acylates C3. The identification of decorating enzymes with different substrate specificities will allow the tailor-made production of novel subsets of MELs. [ABSTRACT FROM AUTHOR]

[Display omitted] • ALC67 belongs to a recently discovered family of novel antiproliferative agents. • A synthetic library of optically pure ferrocenyl analogs of ALC67 was prepared. • Two compounds (6c- cis and 6-d) showed similar cytotoxicity to ALC67 and cisplatin. • The cytotoxicity depended on the electrophilicity of the N -acyl side chain group. • Derivative 6c- cis also manifested a selective anti- Bacillus cereus activity. To improve the antiproliferative effect of ALC67 (diastereomeric mixture of ethyl 2-phenyl-3-propioloyl-1,3-thiazolidine-4-carboxylate), its structure was modified via (i) bioisosteric substitution of the phenyl ring by the ferrocene unit and (ii) replacing the propiolamide side-chain in ACL67 with other acyl groups having differing electrophilicities. In this way, a small library of methyl N -acyl-2-ferrocenyl-1,3-thiazolidine-4-carboxylates (13 compounds in total) was created and characterized by spectral and crystallographic means. The last N -acylation step was highly diastereoselective toward the cis -diastereomer. In solution, most of the obtained compounds existed as a mixture of two rotamers and displayed a preference for the syn -orientation around the C N bond. A twisted 5 T 4 envelope conformation was adopted by the derivative containing the N -phenoxyacetyl group in the crystalline state. Two derivatives with chloroacetyl and bromoacetyl groups in the N -3 side chain were cytotoxic to fibroblasts and hepatocellular cancer cells in the low micromolar range (IC 50 (MRC5) = 9.0 and 11.8 μM, respectively, and IC 50 (HepG2) = 10.6 and 18.4 μM, respectively) causing an effect similar to the lead compound (IC 50 (HepG2) = 10.0 μM) and cisplatin (IC 50 (MRC5) = 4.0 μM and IC 50 (HepG2) = 7.7 μM). Several derivatives also manifested modest antimicrobial effects against the studied microbial strains (MICs in the range from 0.44 to 4.0 μmol/mL). Our findings demonstrated that the introduction of a ferrocene core facilitated the preparation of optically pure analogs of ALC67 and that the cytotoxicity of compounds may be enhanced by adding proper electrophilic centers to the N -acyl side-chain. [ABSTRACT FROM AUTHOR]

1-Acyl- sn -glycerol-3-phosphate O -acyltransferase (PlsC) plays an essential role in the formation of phosphatidic acid, a precursor of various membrane phospholipids (PLs), in bacteria by catalyzing the introduction of an acyl group into the sn -2 position of lysophosphatidic acid. Various bacteria produce more than one PlsC. However, the physiological significance of the occurrence of multiple PlsCs is poorly understood. A psychrotrophic bacterium, Shewanella livingstonensis Ac10, which produces eicosapentaenoic acid at low temperatures, has five putative PlsCs (PlsC1-5). We previously showed that PlsC1 is responsible for the production of PLs containing an eicosapentaenoyl group. Here, we characterized another putative PlsC of this bacterium named PlsC4. We generated a plsC4 -disrupted mutant and found that PLs containing 13:0 found in the parental strain were almost completely absent in the mutant. The loss of these PLs was suppressed by introduction of a plsC4 -expression plasmid. PLs containing 15:0 were also drastically decreased by plsC4 disruption. Gas chromatography-mass spectrometry analysis of fatty acyl methyl esters derived from PLs of the parental strain showed that the 13:0 and 15:0 groups were an 11-methyllauroyl group and a 13-methylmyristoyl group, respectively. Phospholipase A2 treatment revealed that these fatty acyl groups were linked to the sn -2 position of PLs. Thus, PlsC4 is a new type of PlsC homolog that is responsible for the synthesis of PLs containing a branched-chain fatty acyl group at the sn -2 position and plays a clearly different role from that of PlsC1 in vivo . [ABSTRACT FROM AUTHOR]

In this paper, a new resin (PIDTR) containing acyl and thiourea chelating groups was synthesized and its adsorption performances and mechanism to Cu(II) were investigated by adsorption tests, BET, SEM, FTIR and XPS analyses. Equilibrium data were fitted well with Langmuir model with the maximum adsorption capacity of 1.1608 mmol g −1 for Cu(II) at pH 5.0. The regeneration and reusability test showed that the adsorption capacities decreased from 0.917 mmol g −1 to 0.88 mmol g −1 after five cycles of adsorption and desorption. The thermodynamics showed that the adsorption process was spontaneous and endothermic. The adsorption dynamic demonstrated that two stages in the adsorption process: liquid film diffusion and chemical adsorption. The studies of SEM indicated that Cu(II) ions were adsorbed on the surface of PIDTR. FTIR and XPS analysis further proved that Cu(II) ions were chemisorbed on the surface of PIDTR by formation of Cu N, Cu O and Cu S bonds with the breakage of N H, C=O and S=C bonds in PIDTR. [ABSTRACT FROM AUTHOR]

Oilseed cakes obtained by cold-pressing are rich in lipids susceptible to degradation, which could challenge their handling and nutritional, safety, and sensory requirements, especially during long-storage. Although extrusion is effective at reducing antinutritional factors, its effect on the lipid stability of oilseed cakes remains unknown. In this work, a comparative 1H-NMR-based investigation of the lipid quality in terms of lipid composition, hydrolysis, and oxidation status, as well as their stability after long-term storage was performed on soybean, canola and sunflower cold-pressed cakes before and after low-moisture extrusion. Soybean cake was rich in linolenic and linoleic groups, whereas canola and sunflower mostly contained linoleic and monounsaturated acyl groups and fatty acids. Extrusion did not modify lipid quality immediately after processing. Nevertheless, lipid stability was significantly reduced after 12 months, especially in cakes subjected to extrusion, evidenced by the degradation of their polyunsaturated acyl groups and fatty acids, and the increase of primary and secondary oxidation products. Since lipid quality was retained immediately after extrusion (no storage), results indicated that any action to avoid the enzymatic lipid degradation must be performed immediately after cold-pressing. Moreover, long-term storage should be carefully considered as the lipid stability/quality of extruded cakes was compromised after extrusion. • Lipid quality was studied in terms of acyl group profile, hydrolysis, and oxidation. • Cold-pressed cakes contain up to 18% lipids, most of which susceptible to degradation. • NMR showed that extrusion did not modify lipid quality immediately after processing. • Lipid stability was significantly reduced after 12 months, especially after extrusion. [ABSTRACT FROM AUTHOR]

With ageing there is frequently a loss of appetite, termed anorexia of ageing, which can result in under-nutrition. We do not know how appetite control alters with ageing. The objective of this study was to investigate whether differences in the release of, and response to, gastrointestinal appetite hormones is altered in young compared to old healthy volunteers. We hypothesised that an increase in PYY and GLP-1 or a decrease ghrelin may result in a decreased appetite. A comparative experimental design, using a cross-sectional sample of ages from a healthy population, matched for sex and BMI was used. The study compared total ghrelin, acyl-ghrelin, PYY, GLP-1 and subjective appetite responses to ingestion of a standardised 2781kj (660 kcal) test meal. 31 female volunteers aged between 21 and 92yrs took part. Multiple linear regression showed that both age and sex had an independent effect on energy intake. Subjective appetite scores showed that hunger, pleasantness to eat, and prospective food intake were significantly lower in the older age groups. PYY incremental area under the curve (IAUC) was greater in the oldest old compared to younger ages f(3,27) = 2.9, p = 0.05. No differences in GLP-1, ghrelin or acyl-ghrelin were observed in the older compared to younger age groups. Our data suggest that there may be increases in postprandial PYY(3-36) levels in female octogenarians, potentially resulting in reduced appetite. There does not appear to be any change in ghrelin or acyl-ghrelin concentrations with ageing. [ABSTRACT FROM AUTHOR]

Highlights: [•] AAPH induce oxidation in fatty acyl chain and serine headgroup of PS. [•] Parent scan and neutral loss were used for analysis of oxPOPS. [•] Oxidation in the serine headgroup was observed in HaCaT cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] Dioctanoyl-PC (diC8PC) supported growth of a yeast mutant defective in PC synthesis. [•] diC8PC was converted to PC species containing longer acyl residues in the mutant. [•] Both acyl residues of diC8PC were replaced by longer fatty acids in vitro. [•] This system will contribute to the elucidation of the acyl chain remodeling of PC. [ABSTRACT FROM AUTHOR]

Highlights: [•] The Pseudomonas sp. DF41 quorum-sensing system consists of PdfR and PdfI. [•] A gene encoding a novel LuxR-type protein, RfiA, is co-transcribed with pdfI. [•] Quorum sensing indirectly controls DF41 antifungal activity through RfiA. [•] pdfI and acyl homoserine lactone production are positively regulated by the Gac–Rsm system. [ABSTRACT FROM AUTHOR]

Abstract: The generality of acyl transfer from phospholipids to membrane-active peptides has been probed using liquid chromatography–mass spectrometry analysis of peptide–lipid mixtures. The peptides examined include melittin, magainin II, PGLa, LAK1, LAK3 and penetratin. Peptides were added to liposomes with membrane lipid compositions ranging from pure phosphatidylcholine (PC) to mixtures of PC with phosphatidylethanolamine, phosphatidylserine or phosphatidylglycerol. Experiments were typically conducted at pH7.4 at modest salt concentrations (90mM NaCl). In favorable cases, lipidated peptides were further characterized by tandem mass spectrometry methods to determine the sites of acylation. Melittin and magainin II were the most reactive peptides, with significant acyl transfer detected under all conditions and membrane compositions. Both peptides were lipidated at the N-terminus by transfer from PC, phosphatidylethanolamine, phosphatidylserine or phosphatidylglycerol, as well as at internal sites: lysine for melittin; serine and lysine for magainin II. Acyl transfer could be detected within 3h of melittin addition to negatively charged membranes. The other peptides were less reactive, but for each peptide, acylation was found to occur in at least one of the conditions examined. The data demonstrate that acyl transfer is a generic process for peptides bound to membranes composed of diacylglycerophospholipids. Phospholipid membranes cannot therefore be considered as chemically inert toward peptides and by extension proteins. [Copyright &y& Elsevier]

Highlights: [•] Alpha-synuclein binds to lipid droplets in wild-type yeast cells. [•] Alpha-synuclein does not bind to lipid droplets in peroxisome-deficient (pex3Δ) cells. [•] A peroxisome deficiency alters the composition of lipid droplets; acyl chains shorten. [•] The shortened acyl chains contribute to the reduced binding of alpha-synuclein. [ABSTRACT FROM AUTHOR]

• Contents of trans fatty acids in oils was determined by 1H NMR spectroscopy in association with multivariate calibration. • The 1H NMR spectra of edible and cis-trans isomerized oils are different in three chemical shift regions. • The difference of the 1H NMR spectra of cis and tans unsaturated fatty acids was analyzed. • The PLS method were successfully applied to predict the contents of unsaturated fatty acids in oils. In this work, cis and trans fatty acid (FA) contents in edible oils was determined using 1H nuclear magnetic resonance (1H NMR) spectroscopy. The comparison of 1H NMR spectra of edible oil and cis-trans isomerized oil showed that they were different in three regions: (1) 2.880 - 2.650 ppm caused by bis-allylic protons; (2) 2.140 - 1.900 ppm due to allylic protons; and (3) 1.030 - 0.930 ppm due to methyl protons of linolenic acyl groups. The 1H NMR signals in these regions were combined with partial least squares method to predict contents of cis/trans fatty acids in edible oils. The results showed that the predicted values were consistent with the gas chromatography-measured values and had a good linear relationship with a correlation coefficient (R2) of above 0.98. This work demonstrates that 1H NMR spectroscopy was successfully used to determine the composition of both cis and trans fatty acids in edible oils. [ABSTRACT FROM AUTHOR]

Abstract: The origin of N-acyl ethanolamides (NAEs) in plasma is not well understood, and it is possible that NAEs are present in plasma in esterified form. To test this hypothesis, a new and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the quantification of arachidonoyl ethanolamide, 2-arachidonoyl glycerol, docosahexaenoyl ethanolamide, dihomo-γ-linolenoyl ethanolamide, oleoyl ethanolamide, palmitoyl ethanolamide, and stearoyl ethanolamide in 100μl of human plasma using a simple acetonitrile extraction step. Using this method, we determined (i) free and esterified NAE levels in human plasma, (ii) free and esterified NAE levels in plasma of mice fed with diets with different amounts of n-3 fatty acids, and (iii) esterified NAE levels in blood cells. Murine and human plasma extracts contained 20- to 60-fold higher levels of esterified NAEs than free NAEs. Moreover, the effect of dietary n-3 fatty acids on murine free plasma NAE profiles was similar for esterified NAEs. Finally, esterified NAEs were also present in murine blood cells, and their pattern followed the same diet effect as observed for free and esterified NAEs in plasma. Together, these data point to the presence of previously ignored pools of esterified NAEs in plasma and blood cells that correlated well with free NAE levels in plasma. [Copyright &y& Elsevier]

Abstract: We report on two families with Sengers syndrome and mutations in the acylglycerol kinase gene (AGK). In the first family, two brothers presented with vascular strokes, lactic acidosis, cardiomyopathy and cataracts, abnormal muscle cell histopathology and mitochondrial function. One proband had very abnormal mitochondria with citrate synthase crystals visible in electron micrographs, associated with markedly high citrate synthase activity. Exome sequencing was used to identify mutations in the AGK gene in the index patient. Targeted sequencing confirmed the same homozygous mutation (c.3G>A, p.M1I) in the brother. The second family had four affected members, of which we examined two. They also presented with similar clinical symptoms, but no strokes. Postmortem heart and skeletal muscle tissues showed low complex I, III and IV activities in the heart, but normal in the muscle. Skin fibroblasts showed elevated lactate/pyruvate ratios and low complex I+III activity. Targeted sequencing led to identification of a homozygous c.979A>T, p.K327* mutation. AGK is located in the mitochondria and phosphorylates monoacylglycerol and diacylglycerol to lysophosphatidic acid and phosphatidic acid. Disruption of these signaling molecules affects the mitochondria''s response to superoxide radicals, resulting in oxidative damage to mitochondrial DNA, lipids and proteins, and stimulation of cellular detoxification pathways. High levels of manganese superoxide dismutase protein were detected in all four affected individuals, consistent with increased free radical damage. Phosphatidic acid is also involved in the synthesis of phospholipids and its loss will result in changes to the lipid composition of the inner mitochondrial membrane. These effects manifest as cataract formation in the eye, respiratory chain dysfunction and cardiac hypertrophy in heart tissue. These two pedigrees confirm that mutation of AGK is responsible for the severe neonatal presentation of Sengers syndrome. The identification of citrate synthase precipitates by electron microscopy and the presence of vascular strokes in two siblings may expand the cellular and clinical phenotype of this disease. [Copyright &y& Elsevier]

The oxidation process of soybean oil enriching with the phenolic extract of Camellia oleifera seed cake (PE), tertiary butylhydroquinone (TBHQ) and tea polyphenol palmitate (TPP) was evaluated under frying condition with 1H nuclear magnetic resonance (NMR). The results showed that PE and TBHQ could inhibit the degradation of unsaturated acyl groups and reduce the generation rate and concentration of oxidative compounds, with PE having better performance. The hydroperoxides and their associated (Z , E)- and (E , E)-conjugated dienes of soybean oil were only detected at 220 min, and soybean oil with PE had the lower intensity of 1H NMR signals. In addition, the nine individual polyphenols significantly reduced during frying, and only three phenolic acids were detected even after 420 min, although their content was extremely low. All results suggested that phenolic extracts could provide an effective alternative to synthetic antioxidants during the frying process. • Effect of polyphenol on frying performance of soybean oil was studied by 1H NMR. • Degradation of acyl groups was significantly delayed after adding polyphenol. • Polyphenol markedly reduced the concentration of some oxidative compounds. • The content of individual polyphenol significantly reduced during frying. • The antioxidant mechanisms of polyphenols were proposed under frying condition. [ABSTRACT FROM AUTHOR]

In the degumming process of crude soybean oil by phospholipase A 1 (PLA 1), the content of free fatty acids (FFA) in the product increases excessively. In this study, PLA 1 was used to hydrolyse simulated crude soybean oil. It was found that the acyl group at the s n- 2 position migrated to the s n- 1 position, the content of FFA in the oil was as high as 1.26 ± 0.03 g/100 g, and the acyl migration rate was up to 38.9 ± 0.10% after 2.8 h. Under the conditions of H 3 BO 3 addition of 2 g/100 g, pH of 5, enzymatic hydrolysis temperature of 50 °C and enzymatic hydrolysis time of 2 h, the acyl migration rate of s n- 2-HPA was 16.8 ± 0.50%, the content of FFA was 1.14 ± 0.02 g/100 g, and the enzymatic hydrolysis efficiency was increased by 28.57 ± 0.07%. • Sn- 2-HPA is unstable, forms a five-membered ring intermediate, cause acyl migration. • Lone pair electron at s n- 1 site is a key factor affecting the stability of s n- 2-HPA. • H 3 BO 3 forms coordination bond with s n- 1 site, blocking the formation of intermediate. • By adding 2% H 3 BO 3 , FFA content was reduced, enzymolysis efficiency was improved. [ABSTRACT FROM AUTHOR]

Abstract: Specific interactions between the polar head groups of membrane lipids and proteins have been described previously. In contrast, the specificity of the interaction between lipid acyl chains with proteins is less understood. By combining a fatty acid or cholesterol pull-down assay with Western blot analysis or mass spectrometry, we identified transmembrane and cytosolic proteins that bound preferentially to short or long acyl chains or to cholesterol. Thus, this approach allows identification of specific fatty acid–protein or cholesterol–protein interactions. [Copyright &y& Elsevier]

Preadipocyte differentiation and lipid synthesis are critical steps for intramuscular fat (IMF) deposition and lipid metabolism homeostasis. IMF content of beef not only determines the ratio of muscle to adipose, but also determines the beef quality, flavor, and sensory characteristics. Maintaining lipid metabolism homeostasis is the key means of preventing and treating diabetes, obesity, and other metabolic diseases. SIRT6, which is an ADP-ribosyltransferase and NAD+-dependent deacetylase of acetyl and long-chain fatty acyl groups, playing central roles in lipid and glucose metabolism, is closely related to the occurrence of diabetes and obesity caused by overnutrition and aging. This study was based on bovine preadipocyte differentiation and an obese mice model, and comprehensively used transcriptome sequencing (RNA-seq) and morphological identification methods to explore the effects of inhibition of SIRT6 on differentiation and lipid synthesis, and related molecular mechanisms. Additionally, the feedback synergistic regulation of SIRT5 and SIRT6 on differentiation and lipid deposition was analyzed. The results showed that in the differentiation process of bovine preadipocytes, inhibition of SIRT5 significantly promoted SIRT6 expression. In addition, SIRT6 inhibited bovine preadipocyte differentiation and lipid synthesis, cooperating with SIRT5 to decrease lipid deposition, and repressed cell cycle arrest of preadipocytes. Moreover, in vivo verification experiments also obtained consistent results. Furthermore, SIRT6 inhibited preadipocyte differentiation and lipid deposition by activating the adenosine monophosphate activated protein kinase alpha (AMPKα) pathway. The above results provided a novel approach for understanding the functions of SIRT6 in regulating bovine adipocyte differentiation and lipid metabolism, as well as a new target for the treatment of diabetes and obesity in a clinical setting. • SIRT6 inhibited bovine preadipocyte differentiation and lipid synthesis. • SIRT6 cooperated with SIRT5 to decrease lipid deposition in bovine preadipocytes. • SIRT6 repressed differentiation by inhibiting the cycle arrest of bovine preadipocytes. • SIRT6 inhibited preadipocyte differentiation and lipid deposition by activating the AMPKα pathway. • SIRT6 inhibited adipose tissue differentiation and lipid synthesis of obese mice in vivo. [ABSTRACT FROM AUTHOR]