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Journal of Food Science and Technology Aug 2023Medium-chain triglycerides contain medium-chain fatty acid esterified to the glycerol backbone. These MCFA have a shorter chain length and are quickly metabolized in the... (Review)
Review
Medium-chain triglycerides contain medium-chain fatty acid esterified to the glycerol backbone. These MCFA have a shorter chain length and are quickly metabolized in the body serving as an immediate energy source. They are known to have good physiological as well as functional characteristics which help in treating various health disorders. Naturally, they are found in coconut oil, milk fat, and palm kernel oil, and they are synthetically produced by esterification and interesterification reactions. Due to their numerous health benefits, MCT is used as a functional or nutraceutical oil in various food and pharmaceutical formulations. To increase their nutraceutical benefits and food applications MCFA can be used along with polyunsaturated fatty acids in the synthesis of structured lipids. This review aims to provide information about triglycerides of MCFA, structure, metabolism, properties, synthetic routes, intensified synthesis approaches, health benefits, application, and safety of use of MCT in the diet.
PubMed: 35761969
DOI: 10.1007/s13197-022-05499-w -
Nature Jun 2022Branched fatty acid (FA) esters of hydroxy FAs (HFAs; FAHFAs) are recently discovered lipids that are conserved from yeast to mammals. A subfamily, palmitic acid esters...
Branched fatty acid (FA) esters of hydroxy FAs (HFAs; FAHFAs) are recently discovered lipids that are conserved from yeast to mammals. A subfamily, palmitic acid esters of hydroxy stearic acids (PAHSAs), are anti-inflammatory and anti-diabetic. Humans and mice with insulin resistance have lower PAHSA levels in subcutaneous adipose tissue and serum. PAHSA administration improves glucose tolerance and insulin sensitivity and reduces inflammation in obesity, diabetes and immune-mediated diseases. The enzyme(s) responsible for FAHFA biosynthesis in vivo remains unknown. Here we identified adipose triglyceride lipase (ATGL, also known as patatin-like phospholipase domain containing 2 (PNPLA2)) as a candidate biosynthetic enzyme for FAHFAs using chemical biology and proteomics. We discovered that recombinant ATGL uses a transacylation reaction that esterifies an HFA with a FA from triglyceride (TG) or diglyceride to produce FAHFAs. Overexpression of wild-type, but not catalytically dead, ATGL increases FAHFA biosynthesis. Chemical inhibition of ATGL or genetic deletion of Atgl inhibits FAHFA biosynthesis and reduces the levels of FAHFA and FAHFA-TG. Levels of endogenous and nascent FAHFAs and FAHFA-TGs are 80-90 per cent lower in adipose tissue of mice in which Atgl is knocked out specifically in the adipose tissue. Increasing TG levels by upregulating diacylglycerol acyltransferase (DGAT) activity promotes FAHFA biosynthesis, and decreasing DGAT activity inhibits it, reinforcing TGs as FAHFA precursors. ATGL biosynthetic transacylase activity is present in human adipose tissue underscoring its potential clinical relevance. In summary, we discovered the first, to our knowledge, biosynthetic enzyme that catalyses the formation of the FAHFA ester bond in mammals. Whereas ATGL lipase activity is well known, our data establish a paradigm shift demonstrating that ATGL transacylase activity is biologically important.
Topics: Acyltransferases; Adipose Tissue; Animals; Diglycerides; Esterification; Esters; Fatty Acids; Humans; Hydroxy Acids; Insulin Resistance; Mice; Triglycerides
PubMed: 35676490
DOI: 10.1038/s41586-022-04787-x -
Cell Metabolism Dec 2020Hepatic TANK (TRAF family member associated NFκB activator)-binding kinase 1 (TBK1) activity is increased during obesity, and administration of a TBK1 inhibitor reduces...
Hepatic TANK (TRAF family member associated NFκB activator)-binding kinase 1 (TBK1) activity is increased during obesity, and administration of a TBK1 inhibitor reduces fatty liver. Surprisingly, liver-specific TBK1 knockout in mice produces fatty liver by reducing fatty acid oxidation. TBK1 functions as a scaffolding protein to localize acyl-CoA synthetase long-chain family member 1 (ACSL1) to mitochondria, which generates acyl-CoAs that are channeled for β-oxidation. TBK1 is induced during fasting and maintained in the unphosphorylated, inactive state, enabling its high affinity binding to ACSL1 in mitochondria. In TBK1-deficient liver, ACSL1 is shifted to the endoplasmic reticulum to promote fatty acid re-esterification in lieu of oxidation in response to fasting, which accelerates hepatic lipid accumulation. The impaired fatty acid oxidation in TBK1-deficient hepatocytes is rescued by the expression of kinase-dead TBK1. Thus, TBK1 operates as a rheostat to direct the fate of fatty acids in hepatocytes, supporting oxidation when inactive during fasting and promoting re-esterification when activated during obesity.
Topics: Animals; Coenzyme A Ligases; Fatty Acids; HEK293 Cells; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Non-alcoholic Fatty Liver Disease; Obesity; Oxidation-Reduction; Protein Serine-Threonine Kinases
PubMed: 33152322
DOI: 10.1016/j.cmet.2020.10.010 -
Alzheimer's Research & Therapy May 2023The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients.
OBJECTIVE
The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer's disease (AD) patients.
METHODS
The study enrolled 70 AD patients and 74 cognitively normal controls comparable for age and sex. Lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF.
RESULTS
AD patients have normal plasma lipids but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in the plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients' plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ CSF content.
CONCLUSION
Taken together our data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ).
Topics: Humans; Alzheimer Disease; Esterification; High-Density Lipoproteins, Pre-beta; Cholesterol; Biomarkers
PubMed: 37210544
DOI: 10.1186/s13195-023-01241-6 -
The Journal of Experimental Medicine Oct 2021Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons...
Upon demyelinating injury, microglia orchestrate a regenerative response that promotes myelin repair, thereby restoring rapid signal propagation and protecting axons from further damage. Whereas the essential phagocytic function of microglia for remyelination is well known, the underlying metabolic pathways required for myelin debris clearance are poorly understood. Here, we show that cholesterol esterification in male mouse microglia/macrophages is a necessary adaptive response to myelin debris uptake and required for the generation of lipid droplets upon demyelinating injury. When lipid droplet biogenesis is defective, innate immune cells do not resolve, and the regenerative response fails. We found that triggering receptor expressed on myeloid cells 2 (TREM2)-deficient mice are unable to adapt to excess cholesterol exposure, form fewer lipid droplets, and build up endoplasmic reticulum (ER) stress. Alleviating ER stress in TREM2-deficient mice restores lipid droplet biogenesis and resolves the innate immune response. Thus, we conclude that TREM2-dependent formation of lipid droplets constitute a protective response required for remyelination to occur.
Topics: Animals; Cholesterol; Endoplasmic Reticulum Stress; Esterification; Lipid Droplets; Membrane Glycoproteins; Mice, Inbred C57BL; Mice, Knockout; Microglia; Phagocytes; Protein Biosynthesis; Receptors, Immunologic; Remyelination; Sterol O-Acyltransferase; Mice
PubMed: 34424266
DOI: 10.1084/jem.20210227 -
Exploration of Targeted Anti-tumor... 2023Many human cancers carry missense mutations in or deletions of the tumor protein 53 (TP53) tumor suppressor gene. TP53's product, p53 regulates many biological...
Many human cancers carry missense mutations in or deletions of the tumor protein 53 (TP53) tumor suppressor gene. TP53's product, p53 regulates many biological processes, including cell metabolism. Cholesterol is a key lipid needed for the maintenance of membrane function and tissue homeostasis while also serving as a precursor for steroid hormone and bile acid synthesis. An over-abundance of cholesterol can lead to its esterification and storage as cholesterol esters. The recent study has shown that the loss of p53 leads to excessive cholesterol ester biosynthesis, which promotes hepatocellular carcinoma in mice. Blocking cholesterol esterification improves treatment outcomes, particularly for liver cancers with p53 deletions/mutations that originate in a background of non-alcoholic fatty liver disease.
PubMed: 38023993
DOI: 10.37349/etat.2023.00185 -
Non-coding RNA Research Sep 2023Atherosclerosis is a significant risk factor for coronary heart disease (CHD) and myocardial infarction (MI). Atherosclerosis develops during foam cell generation, which... (Review)
Review
Atherosclerosis is a significant risk factor for coronary heart disease (CHD) and myocardial infarction (MI). Atherosclerosis develops during foam cell generation, which is caused by an imbalance in cholesterol uptake, esterification, and efflux. LOX-1, SR-A1, and CD36 all increased cholesterol uptake. ACAT1 and ACAT2 promote free cholesterol (FC) esterification to cholesteryl esters (CE). The hydrolysis of CE to FC was aided by nCEH. FC efflux was promoted by ABCA1, ABCG1, ADAM10, and apoA-I. SR-BI promotes not only cholesterol uptake but also FC efflux. Circular RNAs (circRNAs), which are single-stranded RNAs with a closed covalent circular structure, have emerged as promising biomarkers and therapeutic targets for atherosclerosis due to their highly tissue, cell, and disease state-specific expression profiles. Numerous studies have shown that circRNAs regulate foam cell formation, acting as miRNA sponges to influence atherosclerosis development by regulating the expression of SR-A1, CD36, ACAT2, ABCA1, ABCG1, ADAM10, apoA-I, SR-B1. Several circRNAs, including circ-Wdr91, circ 0004104, circRNA0044073, circRNA_0001805, circDENND1B, circRSF1, circ 0001445, and circRNA 102682, are potential biomarkers for atherosclerosis to better evaluate cardiovascular risk. It is difficult to deliver synthetic therapeutic circRNAs to the desired target tissues. Nanotechnology, such as GA-RM/GZ/PL, may be an important solution to this problem. In this review, we focus on the potential role and mechanism of circRNA/miRNA axis in foam cell formation in the hopes of discovering new targets for the diagnosis, prevention, and treatment of atherosclerosis.
PubMed: 37032721
DOI: 10.1016/j.ncrna.2023.03.005 -
The Plant Cell Dec 2019
Topics: Bread; Esterases; Esterification; Lipase; Lutein; Triticum
PubMed: 31578226
DOI: 10.1105/tpc.19.00768 -
ACS Omega Sep 20201-Palmitoyl- -2-oleoyl- --glycero-3-phosphocholine (POPC- ) with the palmitoyl and oleoyl chains deuterium-labeled was produced in three steps from...
1-Palmitoyl- -2-oleoyl- --glycero-3-phosphocholine (POPC- ) with the palmitoyl and oleoyl chains deuterium-labeled was produced in three steps from 1-palmitoyl-2-hydroxy--glycero-3-phosphocholine, deuterated palmitic acid, and deuterated oleic anhydride. Esterification at the -2 position was achieved under standard chemical conditions, using DMAP to catalyze the reaction between the 2-lysolipid and oleic anhydride- . Complete regioselective -1 acyl substitution was achieved in two steps using operationally simple, enzyme-catalyzed regioselective hydrolysis and esterification to substitute the -1 chain for a perdeuterated analogue. This method provides chain-deuterated POPC with high chemical purity (>96%) and complete regiopurity, useful for a variety of experimental techniques. This chemoenzymatic semisynthetic approach is a general, modular method of producing highly pure, mixed-acyl phospholipids, where the advantages of both chemical synthesis (efficiency, high yields) and biocatalytic synthesis (specificity, nontoxicity) are realized.
PubMed: 32923797
DOI: 10.1021/acsomega.0c02823 -
Molecules (Basel, Switzerland) Jan 2023With incidence of antimicrobial resistance rising globally, there is a continuous need for development of new antimicrobial molecules. Phenolic compounds having a... (Review)
Review
With incidence of antimicrobial resistance rising globally, there is a continuous need for development of new antimicrobial molecules. Phenolic compounds having a versatile scaffold that allows for a broad range of chemical additions; they also exhibit potent antimicrobial activities which can be enhanced significantly through functionalization. Synthetic routes such as esterification, phosphorylation, hydroxylation or enzymatic conjugation may increase the antimicrobial activity of compounds and reduce minimal concentrations needed. With potent action mechanisms interfering with bacterial cell wall synthesis, DNA replication or enzyme production, phenolics can target multiple sites in bacteria, leading to a much higher sensitivity of cells towards these natural compounds. The current review summarizes some of the most important knowledge on functionalization of natural phenolic compounds and the effects on their antimicrobial activity.
Topics: Anti-Infective Agents; Phenols; Plant Extracts; Antioxidants; Anti-Bacterial Agents
PubMed: 36770780
DOI: 10.3390/molecules28031114