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Ultrasonics Sonochemistry May 2023The study aimed to evaluate the effect of ultrasonic pretreatment on the transesterification of lard with glycerol monolaurate (GML) using Lipozyme TL IM to synthesize... (Review)
Review
The study aimed to evaluate the effect of ultrasonic pretreatment on the transesterification of lard with glycerol monolaurate (GML) using Lipozyme TL IM to synthesize diacylglycerol (DAG), and the physicochemical properties of lard, GML, ultrasonic-treated diacylglycerol (named U-DAG), purified ultrasonic-treated diacylglycerol obtained by molecular distillation (named P-U-DAG), and without ultrasonic-treated diacylglycerol (named N-U-DAG) were analyzed. The optimized ultrasonic pretreatment conditions were: lard to GML mole ratio 3:1, enzyme dosage 6 %, ultrasonic temperature 80 °C, time 9 min, power 315 W. After ultrasonic pretreatment, the mixtures reacted for 4 h in a water bath at 60 °C, the content of DAG reached 40.59 %. No significant variations were observed between U-DAG and N-U-DAG in fatty acids compositions and iodine value, while P-U-DAG had lower unsaturated fatty acids than U-DAG. Differential scanning calorimetry analysis showed that the melting and crystallization properties of DAGs prepared by ultrasonic pretreatment significantly differed from lard. FTIR spectra noted transesterification reaction from lard and GML with and without ultrasonic pretreatment would not change the structure of lard. However, thermogravimetric analysis proved that N-U-DAG, U-DAG, and P-U-DAG had lower oxidation stability than lard. The higher the content of DAG, the faster the oxidation speed.
Topics: Diglycerides; Dietary Fats; Catalysis; Glycerol
PubMed: 36898248
DOI: 10.1016/j.ultsonch.2023.106354 -
Cell and Tissue Research Jan 2016Mammalian embryo development begins when the fertilizing sperm triggers a series of elevations in the oocyte's intracellular free Ca(2+) concentration. The elevations... (Review)
Review
Mammalian embryo development begins when the fertilizing sperm triggers a series of elevations in the oocyte's intracellular free Ca(2+) concentration. The elevations are the result of repeated release and re-uptake of Ca(2+) stored in the smooth endoplasmic reticulum. Ca(2+) release is primarily mediated by the phosphoinositide signaling system of the oocyte. The system is stimulated when the sperm causes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG); IP3 then binds its receptor on the surface of the endoplasmic reticulum that induces Ca(2+) release. The manner in which the sperm generates IP3, the Ca(2+) mobilizing second messenger, has been the subject of extensive research for a long time. The sperm factor hypothesis has eventually gained general acceptance, according to which it is a molecule from the sperm that diffuses into the ooplasm and stimulates the phosphoinositide cascade. Much evidence now indicates that the sperm-derived factor is phospholipase C-zeta (PLCζ) that cleaves PIP2 and generates IP3, eventually leading to oocyte activation. A recent addition to the candidate sperm factor list is the post-acrosomal sheath WW domain-binding protein (PAWP), whose role at fertilization is currently under debate. Ca(2+) influx across the plasma membrane is also important as, in the absence of extracellular Ca(2+), the oscillations run down prematurely. In pig oocytes, the influx that sustains the oscillations seems to be regulated by the filling status of the stores, whereas in the mouse other mechanisms might be involved. This work summarizes the current understanding of Ca(2+) signaling in mammalian oocytes.
Topics: Animals; Calcium Signaling; Diglycerides; Female; Fertilization; Humans; Inositol 1,4,5-Trisphosphate; Male; Oocytes; Signal Transduction; Sperm-Ovum Interactions; Spermatozoa; Type C Phospholipases
PubMed: 26453398
DOI: 10.1007/s00441-015-2291-8 -
PLoS Medicine Feb 2024Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects...
BACKGROUND
Emulsifiers are widely used food additives in industrially processed foods to improve texture and enhance shelf-life. Experimental research suggests deleterious effects of emulsifiers on the intestinal microbiota and the metabolome, leading to chronic inflammation and increasing susceptibility to carcinogenesis. However, human epidemiological evidence investigating their association with cancer is nonexistent. This study aimed to assess associations between food additive emulsifiers and cancer risk in a large population-based prospective cohort.
METHODS AND FINDINGS
This study included 92,000 adults of the French NutriNet-Santé cohort without prevalent cancer at enrolment (44.5 y [SD: 14.5], 78.8% female, 2009 to 2021). They were followed for an average of 6.7 years [SD: 2.2]. Food additive emulsifier intakes were estimated for participants who provided at least 3 repeated 24-h dietary records linked to comprehensive, brand-specific food composition databases on food additives. Multivariable Cox regressions were conducted to estimate associations between emulsifiers and cancer incidence. Overall, 2,604 incident cancer cases were diagnosed during follow-up (including 750 breast, 322 prostate, and 207 colorectal cancers). Higher intakes of mono- and diglycerides of fatty acids (FAs) (E471) were associated with higher risks of overall cancer (HR high vs. low category = 1.15; 95% CI [1.04, 1.27], p-trend = 0.01), breast cancer (HR = 1.24; 95% CI [1.03, 1.51], p-trend = 0.04), and prostate cancer (HR = 1.46; 95% CI [1.09, 1.97], p-trend = 0.02). In addition, associations with breast cancer risk were observed for higher intakes of total carrageenans (E407 and E407a) (HR = 1.32; 95% CI [1.09, 1.60], p-trend = 0.009) and carrageenan (E407) (HR = 1.28; 95% CI [1.06, 1.56], p-trend = 0.01). No association was detected between any of the emulsifiers and colorectal cancer risk. Several associations with other emulsifiers were observed but were not robust throughout sensitivity analyses. Main limitations include possible exposure measurement errors in emulsifiers intake and potential residual confounding linked to the observational design.
CONCLUSIONS
In this large prospective cohort, we observed associations between higher intakes of carrageenans and mono- and diglycerides of fatty acids with overall, breast and prostate cancer risk. These results need replication in other populations. They provide new epidemiological evidence on the role of emulsifiers in cancer risk.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03335644.
Topics: Adult; Male; Humans; Diet; Risk Factors; Prospective Studies; Food Additives; Diglycerides; Breast Neoplasms; Prostatic Neoplasms; Fatty Acids
PubMed: 38349899
DOI: 10.1371/journal.pmed.1004338 -
International Journal of Molecular... Jul 2020An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases... (Review)
Review
An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases (DGKs) are very active in the PI cycle. They are a family of ten members that convert diacylglycerol (DAG) into phosphatidic acid (PA), two-second messengers with versatile cellular functions. Notably, some DGK isoforms, such as DGKα, have been reported to possess promising therapeutic potential in cancer therapy. However, further studies are needed in order to better comprehend their involvement in cancer. In this review, we highlight that DGKs are an essential component of the PI cycle that localize within several subcellular compartments, including the nucleus and plasma membrane, together with their PI substrates and that they are involved in mediating major cancer cell mechanisms such as growth and metastasis. DGKs control cancer cell survival, proliferation, and angiogenesis by regulating Akt/mTOR and MAPK/ERK pathways. In addition, some DGKs control cancer cell migration by regulating the activities of the Rho GTPases Rac1 and RhoA.
Topics: Animals; Cell Movement; Diacylglycerol Kinase; Diglycerides; Humans; MAP Kinase Signaling System; Neoplasm Proteins; Neoplasms
PubMed: 32722576
DOI: 10.3390/ijms21155297 -
Biochimica Et Biophysica Acta.... Jan 2020In yeast and higher eukaryotes, phospholipids and triacylglycerol are derived from phosphatidate at the nuclear/endoplasmic reticulum membrane. In de novo biosynthetic... (Review)
Review
In yeast and higher eukaryotes, phospholipids and triacylglycerol are derived from phosphatidate at the nuclear/endoplasmic reticulum membrane. In de novo biosynthetic pathways, phosphatidate is channeled into membrane phospholipids via its conversion to CDP-diacylglycerol. Its dephosphorylation to diacylglycerol is required for the synthesis of triacylglycerol as well as for the synthesis of phosphatidylcholine and phosphatidylethanolamine via the Kennedy pathway. In addition to the role of phosphatidate as a precursor, it is a regulatory molecule in the transcriptional control of phospholipid synthesis genes via the Henry regulatory circuit. Pah1 phosphatidate phosphatase and Dgk1 diacylglycerol kinase are key players that function counteractively in the control of the phosphatidate level at the nuclear/endoplasmic reticulum membrane. Loss of Pah1 phosphatidate phosphatase activity not only affects triacylglycerol synthesis but also disturbs the balance of the phosphatidate level, resulting in the alteration of lipid synthesis and related cellular defects. The pah1Δ phenotypes requiring Dgk1 diacylglycerol kinase exemplify the importance of the phosphatidate level in the misregulation of cellular processes. The catalytic function of Pah1 requires its translocation from the cytoplasm to the nuclear/endoplasmic reticulum membrane, which is regulated through its phosphorylation in the cytoplasm by multiple protein kinases as well as through its dephosphorylation by the membrane-associated Nem1-Spo7 protein phosphatase complex. This article is part of a Special Issue entitled Endoplasmic reticulum platforms for lipid dynamics edited by Shamshad Cockcroft and Christopher Stefan.
Topics: Animals; Diacylglycerol Kinase; Diglycerides; Endoplasmic Reticulum; Humans; Lipogenesis; Nuclear Envelope; Phosphatidate Phosphatase; Phospholipids; Triglycerides
PubMed: 30910690
DOI: 10.1016/j.bbalip.2019.03.006 -
Molecules (Basel, Switzerland) Oct 2022The drastic increase in the number of patients with diabetes and its complications is a global issue. Diabetic nephropathy, the leading cause of chronic kidney disease,... (Review)
Review
The drastic increase in the number of patients with diabetes and its complications is a global issue. Diabetic nephropathy, the leading cause of chronic kidney disease, significantly affects patients' quality of life and medical expenses. Furthermore, there are limited drugs for treating diabetic nephropathy patients. Impaired lipid signaling, especially abnormal protein kinase C (PKC) activation by de novo-synthesized diacylglycerol (DG) under high blood glucose, is one of the causes of diabetic nephropathy. DG kinase (DGK) is an enzyme that phosphorylates DG and generates phosphatidic acid, i.e., DGK can inhibit PKC activation under diabetic conditions. Indeed, it has been proven that DGK activation ameliorates diabetic nephropathy. In this review, we summarize the involvement of PKC and DGK in diabetic nephropathy as therapeutic targets, and its mechanisms, by referring to our recent study.
Topics: Humans; Diacylglycerol Kinase; Diabetic Nephropathies; Diglycerides; Blood Glucose; Quality of Life; Phosphatidic Acids; Protein Kinase C; Diabetes Mellitus
PubMed: 36296376
DOI: 10.3390/molecules27206784 -
Lifestyle Genomics 2023Rate-limiting enzymes (RLEs) are innate slow points in metabolic pathways, and many function in bio-processes related to nutrient sensing. Many RLEs carry causal...
INTRODUCTION
Rate-limiting enzymes (RLEs) are innate slow points in metabolic pathways, and many function in bio-processes related to nutrient sensing. Many RLEs carry causal mutations relevant to inherited metabolic disorders. Because the activity of RLEs in cardiovascular health is poorly characterized, our objective was to assess their involvement in cardiometabolic health and disease and where altered biophysical and biochemical functions can promote disease.
METHODS
A dataset of 380 human RLEs was compared to protein and gene datasets for factors likely to contribute to cardiometabolic disease, including proteins showing significant age-related altered expression in blood and genetic loci with variants that associate with common cardiometabolic phenotypes. The biochemical reactions catalyzed by RLEs were evaluated for metabolites enriched in RLE subsets associating with various cardiometabolic phenotypes. Most significance tests were based on Z-score enrichment converted to p values with a normal distribution function.
RESULTS
Of 380 RLEs analyzed, 112 function in mitochondria, and 53 are assigned to inherited metabolic disorders. There was a depletion of RLE proteins known as aging biomarkers. At the gene level, RLEs were assessed for common genetic variants that associated with important cardiometabolic traits of LDL-cholesterol or any of the five outcomes pertinent to metabolic syndrome. This revealed several RLEs with links to cardiometabolic traits, from a minimum of 26 for HDL-cholesterol to a maximum of 45 for plasma glucose. Analysis of these GWAS-linked RLEs for enrichment of the molecular constituents of the catalyzed reactions disclosed a number of significant phenotype-metabolite links. These included blood pressure with acetate (p = 2.2 × 10-4) and NADP+ (p = 0.0091), plasma HDL-cholesterol and triglyceride with diacylglycerol (p = 2.6 × 10-5, 6.4 × 10-5, respectively) and diolein (p = 2.2 × 10-6, 5.9 × 10-6), and waist circumference with
d -glucosamine-6-phosphate (p = 1.8 × 10-4).CONCLUSION
In the context of cardiometabolic health, aging, and disease, these results highlight key diet-derived metabolites that are central to specific rate-limited processes that are linked to cardiometabolic health. These metabolites include acetate and diacylglycerol, pertinent to blood pressure and triglycerides, respectively, as well as diacylglycerol and HDL-cholesterol.
Topics: Humans; Diglycerides; Cardiovascular Diseases; Triglycerides; Cholesterol, HDL; Metabolic Diseases; Aging; Acetates
PubMed: 37473740
DOI: 10.1159/000531350 -
Trends in Pharmacological Sciences Jul 2017Although ample evidence links hepatic lipid accumulation with hepatic insulin resistance, the mechanistic basis of this association is incompletely understood and... (Review)
Review
Although ample evidence links hepatic lipid accumulation with hepatic insulin resistance, the mechanistic basis of this association is incompletely understood and controversial. Diacylglycerols (DAGs) and ceramides have emerged as the two best-studied putative mediators of lipid-induced hepatic insulin resistance. Both lipids were first associated with insulin resistance in skeletal muscle and were subsequently hypothesized to mediate insulin resistance in the liver. However, the putative roles for DAGs and ceramides in hepatic insulin resistance have proved more complex than originally imagined, with various genetic and pharmacologic manipulations yielding a vast and occasionally contradictory trove of data to sort. In this review we examine the state of this field, turning a critical eye toward both DAGs and ceramides as putative mediators of lipid-induced hepatic insulin resistance.
Topics: Animals; Ceramides; Diglycerides; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease
PubMed: 28551355
DOI: 10.1016/j.tips.2017.04.004 -
Disease Models & Mechanisms Nov 2022Xanthohumol (XN) improves cognition of wild-type rodents on a high-fat diet (HFD). Bile acids and ceramide levels in the liver and hippocampus might be linked to these...
Xanthohumol (XN) improves cognition of wild-type rodents on a high-fat diet (HFD). Bile acids and ceramide levels in the liver and hippocampus might be linked to these effects. XN modulates activity of the nuclear farnesoid X receptor (FXR; also known as NR1H4), the primary receptor for bile acids. To determine the role of FXR in the liver and intestine in mediating the effects of XN on cognitive performance, mice with intestine- and liver-specific FXR ablation (FXRIntestine-/- and FXRLiver-/-, respectively) on an HFD or an HFD containing XN were cognitively tested. XN improved cognitive performance in a genotype- and sex-dependent manner, with improved task learning in females (specifically wild-type), reversal learning in males (specifically wild-type and FXRIntestine-/- mutant) and spatial learning (both sexes). XN increased hippocampal diacylglycerol and sphingomyelin levels in females but decreased them in males. XN increased the ratio of shorter-chain to longer-chain ceramides and hexaceramides. Higher diacylglycerol and lower longer-chain ceramide and hexaceramide levels were linked to improved cognitive performance. Thus, the beneficial sex-dependent cognitive effects of XN are linked to changes in hippocampal diacylglycerol and ceramide levels. This article has an associated First Person interview with the first author of the paper.
Topics: Male; Mice; Animals; Diet, High-Fat; Diglycerides; Liver; Bile Acids and Salts; Ceramides; Cognition; Mice, Inbred C57BL
PubMed: 36353888
DOI: 10.1242/dmm.049820 -
Journal of Lipid Research Oct 2015Phospholipases are widely occurring and can be found in several different organisms, including bacteria, yeast, plants, animals, and viruses. Phospholipase C (PLC) is a... (Review)
Review
Phospholipases are widely occurring and can be found in several different organisms, including bacteria, yeast, plants, animals, and viruses. Phospholipase C (PLC) is a class of phospholipases that cleaves phospholipids on the diacylglycerol (DAG) side of the phosphodiester bond producing DAGs and phosphomonoesters. Among PLCs, phosphoinositide-specific PLC (PI-PLC) constitutes an important step in the inositide signaling pathways. The structures of PI-PLC isozymes show conserved domains as well as regulatory specific domains. This is important, as most PI-PLCs share a common mechanism, but each of them has a peculiar role and can have a specific cell distribution that is linked to a specific function. More importantly, the regulation of PLC isozymes is fundamental in health and disease, as there are several PLC-dependent molecular mechanisms that are associated with the activation or inhibition of important physiopathological processes. Moreover, PI-PLC alternative splicing variants can play important roles in complex signaling networks, not only in cancer but also in other diseases. That is why PI-PLC isozymes are now considered as important molecules that are essential for better understanding the molecular mechanisms underlying both physiology and pathogenesis, and are also potential molecular targets useful for the development of innovative therapeutic strategies.
Topics: Alternative Splicing; Animals; Diglycerides; Enzyme Activation; Humans; Phosphatidylinositols; Phosphoinositide Phospholipase C; Signal Transduction
PubMed: 25821234
DOI: 10.1194/jlr.R057984