Acid Moiety Research Articles

Pyridylboronic Acid- and Poly(ethylene glycol)-Functionalized PEDOT Copolymers for Electrochemical Detection of Sialic Acid-Rich Cancer Biomarkers in Serum.

The detection of carbohydrate antigen 19-9 (CA199), a critical biomarker for pancreatic, colorectal, and gastric cancers, is essential for early diagnosis and disease monitoring. Traditional antibody-based assays for CA199 detection are limited by high costs, time-consuming procedures, and susceptibility to nonspecific interference. This study presents an electrochemical biosensor based on a multifunctional poly(EDOT-PyBA-co-EDOT-PEG) copolymer designed to overcome these limitations. The biosensor integrates pyridylboronic acid (PyBA) moieties for specific recognition of sialic acid residues and poly(ethylene glycol) (PEG) chains for antifouling properties within a conductive PEDOT framework. By eliminating antibody dependency, the biosensor reduces costs, enhances stability, and simplifies the diagnostic process. Surface characterization confirmed the successful incorporation of PyBA and PEG units, while electrochemical impedance spectroscopy enabled sensitive detection of CA199 with a limit of detection of 0.05 U·mL-1 and a linear response range from 0.05 to 40 U·mL-1. Recovery tests in spiked human serum samples demonstrated excellent accuracy (97-109% recovery), validating the biosensor's reliability in complex biological matrices. The rationally designed copolymer provides both high sensitivity and specificity while maintaining resistance to biofouling in serum samples. This work establishes a scalable, cost-effective platform for glycoprotein biomarker detection, advancing the field of clinical diagnostics and cancer monitoring.

Jejupeptins A and B: Polyketide-Cyclic Peptide Hybrids with Anti-Corticosterone Activity from Streptomyces sp. KCB15JA151.

Two new polyketide-cyclic peptide hybrids jejupeptins A (1) and B (2), together with a known compound eurystatin B (3), were isolated from a culture of Streptomyces sp. KCB15JA151. The chemical structures of the compounds were elucidated using a combination of 1D and 2D NMR spectroscopy and DP4+ probability analyses. Comprehensive spectroscopic analysis revealed that 1 and 2 are the first examples of hybrid peptide-polyketides possessing an unprecedented 4-amino-3-hydroxymethyl-3-methyl-2-oxopentanoic acid moiety. A plausible biosynthetic pathway for these compounds was proposed. Biological evaluation demonstrated that compounds 1 and 2 exhibit protective effects against corticosterone-induced apoptosis and cellular oxidative stress without any associated cytotoxicity.

A Bio-Redox Dynamic Pickering Emulsion from Nature to Nature.

The biosafety issue of Pickering emulsions has gradually become public. It is shown that the particles that make up Pickering emulsions, previously thought to be non-physiologically toxic, may also pose a potential threat to human life and health, as well as to ecosystems, due to their inherent emulsifying capacity. Hence, the principle of "from nature to nature" is proposed, which refers to emulsifiers that are of natural origin and can be metabolized by natural biological processes to eliminate their emulsifying ability. A feasible pathway by which the natural small molecule, thioctic acid, is exploited for the preparation of Pickering emulsions is also presented. The strategy of calcium ion-induced aggregation and ring-opening polymerization of sodium thioctate is utilized for the preparation of particulate emulsifiers, thus forming stable O/W-type Pickering emulsions. Benefiting from the antioxidant property of the thioctic acid moiety and the transdermal capacity of the emulsion itself, it combines protection of the bioactive substance with transdermal delivery. Furthermore, the particulate emulsifiers that are prepared, abundantly enriched with dynamic disulfide bonds, can be integrated into the natural metabolic pathway, specifically by being reduced through the involved glutathione, thereby facilitating their natural degradation and effectively mitigating any potential biological hazards.

Sex Pheromone of the Papaya Mealybug

Sex pheromones of mealybugs are reported from more than 20 species and have generally been shown to be monoterpene alcohols esterified with short-chain carboxylic acids. Here, however, we discovered and isolated an alcohol without an acid moiety as a pheromone compound released from adult females of the papaya mealybug, Paracoccus marginatus. By means of gas chromatography – mass spectrometry and nuclear magnetic resonance spectroscopy analyses, the structure was identified to be trans-2-(2-isopropenyl-1-methylcyclobutyl)ethanol, a monoterpene with a unique cyclobutene skeleton, commonly known as fragranol. We then completely separated synthetic (±)-fragranol into each enantiomer by means of preparative high-performance liquid chromatography using a chiral resolution column, and (−)-(1S,2S)-fragranol was definitely confirmed to be the natural pheromone and to attract many males in the field when used as a pheromone trap lure. (±)-Fragranol showed attractiveness comparable to that of the pure (−)-(1S,2S)-enantiomer. This study provides not only useful information for the monitoring and management of P. marginatus but also an interesting exception underlining the great diversity of mealybug pheromone structures.

Phosphonylated tyrosine and cysteine disulfide adducts both generated from immunoglobulin G and human serum albumin indicate exposure to the nerve agent VX in vitro.

Pronase-catalyzed proteolysis is shown to produce single amino acid adducts of tyrosine (Tyr) and cysteine (Cys) obtained from both human serum albumin (HSA) and immunoglobulin G (IgG) after in vitro exposure of plasma to the nerve agent VX. Total plasma as well as isolated HSA and IgG yielded the Tyr residue phosphonylated with the ethyl methylphosphonic acid moiety, Tyr(-EMP). Furthermore, a Cys residue adducted with the diisopropylaminoethane thiol leaving group of the agent bound via a disulfide bridge, Cys(-DPAET), was also obtained from both proteins. Even though Tyr(-EMP) represents an internationally well-accepted biomarker of a VX-like agent its origin from plasma IgG has never been shown before. In addition, this is the first time that Cys(-DPAET) is presented as a biomarker of VX exposure clearly identifying the chemical nature of the V-type nerve agent's leaving group. Both biomarkers were detected after selective affinity-based solid-phase extraction (SPE) from plasma that yielded highly purified HSA and IgG as documented by sodium dodecyl polyamide gel electrophoresis (SDS-PAGE). Both biomarkers were found in the corresponding protein bands of HSA and IgG each after in-gel proteolysis with pronase. A micro liquid chromatography-electrospray ionization high-resolution tandem-mass spectrometry method (LC-ESI HR-MS/MS) was developed for the simultaneous detection of Tyr(-EMP) and Cys(-DPAET). The time for proteolysis was optimized for maximum biomarker yield. The method showed excellent selectivity and sensitivity, and the adducted proteins and biomarkers were found to be highly stable during storage. Accordingly, the presented method sheds more light on the molecular toxicology of VX and broadens the spectrum of methods suited for biomedical verification.

Stereoselective Synthesis and Antimicrobial Studies of Allo-Gibberic Acid-Based 2,4-Diaminopyrimidine Chimeras

Background: Gibberellins (GAs) are a family of tetracyclic ent-kaurenoid diterpenes found widely in several commonly used plants. Besides agricultural applications, gibberellins play an important role in the synthesis of bioactive compounds, especially those with antiproliferative and antibacterial activity. Methods: A series of gibberellic acid-based 2,4-diaminopyrimidines was designed and synthesized from commercially available gibberellic acid. The antimicrobial activity of the prepared compounds was also explored in B. subtilis, S. aureus, E. coli, and P. aeruginosa bacteria, as well as in C. krusei and C. albicans fungi. Results: The treatment of gibberellic acid with hydrochloric acid under reflux conditions resulted in aromatization followed by rearrangement to form allo-gibberic acid. The key intermediate azido alcohol was prepared according to the literature methods. The second key intermediate azidotriol was synthesized by the stereoselective dihydroxylation of the allylic function by the osmium (VIII)-tetroxide/NMO system. Starting from azide intermediates, click reactions were also carried out with 4-monoamino- and 2,4-diaminopyrimidines functionalized with the N-propargyl group. The new chimeric compounds, coupled with gibberellins thus obtained, were characterized by 1D- and 2D-NMR techniques and HRMS measurements. While the 4-monoamino-substituted derivatives exhibited only weak antibacterial activity, they demonstrated significant antifungal effectiveness against C. krusei. In general, 5-chloro-substituted pyrimidine derivatives displayed more consistent biological activities compared to their 5-fluoro counterparts, with the exception of one derivative, which showed acceptable activity against both C. krusei and C. albicans. The two derivatives featuring 5-chloro and 2-((4-(trifluoromethyl)phenyl)amino substituents proved to be highly effective against P. aeruginosa, making them promising candidates for further research. Aiming to elucidate the molecular interactions between the active compounds and their potential targets, molecular docking studies were conducted using AutoDock Vina 1.1.2. involving the most active compounds against P. aeruginosa. Conclusions: The biological effects of 2-monoamino or 2,4-diamino substitution as well as the effect of chloro or fluoro substitution at position 5 of the pyrimidine ring combined with the allo-gibberic acid moiety were determined. Compounds with selective antibacterial activity against P. aeruginosa as well as selective antifungal activity against C. krusei and C. albicans fungi were identified.

Functional Characterization of Two Polymerizing Glycosyltransferases for the Addition of N-Acetyl-d-galactosamine to the Capsular Polysaccharide of Campylobacter jejuni.

The exterior surface of the human pathogen Campylobacter jejuni is coated with a capsular polysaccharide (CPS) that consists of a repeating sequence of 2-5 different sugars that can be modified with various molecular decorations. In the HS:2 serotype from strain NCTC 11168, the repeating unit within the CPS is composed of d-ribose, N-acetyl-d-galactosamine, and a d-glucuronic acid that is further amidated with either serinol or ethanolamine. The d-glucuronic acid moiety is also decorated with d-glycero-l-gluco-heptose. Here, we show that two different GT2 glycosyltransferases catalyze the transfer of N-acetyl-d-galactosamine from UDP-NAc-d-galactosamine furanoside to the C4-hydroxyl group of the d-glucuronamide moiety at the growing end of the capsular polysaccharide chain. Catalytic activity was not observed with glycosides of d-glucuronic acid, and thus, the C6-carboxylate of the d-glucuronic acid moiety must be amidated prior to chain elongation. One of these enzymes comprises the N-terminal domain of Cj1438 (residues 1-325) and the other is from the N-terminal domain of Cj1434 (residues 1-327). These two glycosyltransferases are ∼87% identical in sequence, but it is not clear why there are two glycosyltransferases from the same gene cluster that apparently catalyze the same reaction. This discovery represents the second polymerizing glycosyltransferase that has been isolated and functionally characterized for the biosynthesis of the capsular polysaccharide in the HS:2 serotype of C. jejuni.

Squaric Acid-Containing Hole-Collecting Monolayer Materials for p-i-n Perovskite Solar Cells.

The development of hole-collecting materials is indispensable to improving the performance of perovskite solar cells (PSCs). To date, several anchorable molecules have been reported as effective hole-collecting monolayer (HCM) materials for p-i-n PSCs. However, their structures are limited to well-known electron-donating skeletons, such as carbazole, triarylamine, etc. In this work, we developed a series of squaraine derivatives that have a π-conjugated core composed of a squaric acid moiety connected to an indoline moiety. Thanks to the polar carbonyl group of squaric acid, all of the molecules were found to form hydrophilic monolayers after being chemisorbed on transparent conducting oxide surfaces, which is beneficial for the subsequent deposition of the perovskite layer. The effect of the substituents on the squaric acid moiety and the anchoring groups connected to the indoline moiety on the molecular electronic structure as well as the solar cell device's performance was elucidated. The p-i-n PSC devices fabricated by using these squaraine derivatives as hole-collecting monolayer materials exhibited high power conversion efficiencies of up to 22.1%, together with good stability. This work highlights the potential of a simple squaric acid skeleton as the building block for hole-collecting monolayer materials to realize high-efficiency and cost-effective PSCs.

A Unique Case of 'in Situ' Bifluoride Triggered Formation of Supramolecular Organogels Using Isophthalamide Hydrogen Bond Donating Receptors.

A novel isopthalamide based receptor H2L2 featuring two p-benzoic acid units has been synthesised and its anion binding properties analysed by 1H-NMR spectroscopy in DMSO-d6/0.5 % H2O. As expected, in the presence of tetrabutylammonium (TBA) fluoride the deprotonation of the carboxylic acid moieties was observed. However, the deprotonated receptor L22- was able to bind the in situ formed HF2 - via the formation of H-bonds with the amide NHs. When H2L2 was dissolved in THF and 4 equivalents of TBAF were added in CH3CN a unique sol-gel transition occurred giving rise to a stable thixotropic supramolecular gel. Theoretical calculations elucidated the gelation mechanism and strongly support the findings observed experimentally.

Engineering of acyl ligase domain in non-ribosomal peptide synthetases to change fatty acid moieties of lipopeptides

Cyclic lipopeptides (CLPs) produced by the genus Bacillus are amphiphiles composed of hydrophilic amino acid and hydrophobic fatty acid moieties and are biosynthesised by non-ribosomal peptide synthetases (NRPSs). CLPs are produced as a mixture of homologues with different fatty acid moieties, whose length affects CLP activity. Iturin family lipopeptides are a family of CLPs comprising cyclic heptapeptides and β-amino fatty acids and have antimicrobial activity. There is little research on how the length of the fatty acid moiety of iturin family lipopeptides is determined. Here, we demonstrated that the acyl ligase (AL) domain determines the length of the fatty acid moiety in vivo. In addition, enzyme assays revealed how mutations in the substrate-binding pocket of the AL domain affected substrate specificity in vitro. Our findings have implications for the design of fatty acyl moieties for CLP synthesis using NRPS.

Copper‐Mediated C−C Coupling of Alkenyl Boronates and Bromodifluoroacetates

AbstractThe reaction of alkenyl boronates and bromodifluoroacetates in the presence of copper powder and TMEDA as the catalytic system was developed. The corresponding C−C coupling products were obtained in 35–93% yield. The method tolerated a variety of functional groups, namely, phenol, (thio)ether, protected amino‐, hydroxy‐, ketone, and carboxylic acid moieties, as well as various saturated carbo‐ and heterocycles, and was compatible with multigram scale‐up (to 76 g). The diastereoselectivity of the process was typically low so that ca. 1:1 E/Z isomeric mixtures were formed from pure E or Z alkenyl boronates. Further functional group transformations demonstrated the utility of the prepared compounds as valuable building blocks for synthetic and medicinal chemistry. Based on the obtained results and the literature data, a plausible reaction mechanism was proposed involving the formation of radical and organocopper intermediates.

PH- and Saccharide-Responsive Cyclometalated Iridium(III) Complexes with Boronic Acid Moieties Displaying a Wide Range of Phosphorescence Colors.

Single compounds displaying a wide range of luminescent colors are attractive optical materials for sensor applications. In this study, we present the beneficial combination of a cyclometalated iridium(III) complex scaffold and boronic acid units for designing stimulus-responsive luminescent materials with various emission colors. Five iridium(III) complexes bearing a diboronic acid ligand (bpyB2) were synthesized: Ir(C^N)bpyB2 (C^N=2-phenylpyridine (1), 2-(2,4-difluorophenyl)pyridine (2), 2-(4-methoxyphenyl)pyridine (3), benzo[h]quinoline (4), 1-phenylisoquinoline (5)). The luminescence color of Complexes 1-4 changed in response to the solution pH or saccharide concentration. Complex 1 exhibited a color change from orange to green-blue due to structural alteration of the boronic acid moiety from trigonal to tetrahedral. Furthermore, the luminescence color of Complex 1 changed reversibly due to repetitive changes in the solution pH between 5 and 10, enabling tuning of the luminescence color and pH tracking. Furthermore, the color range was tuned by selecting an appropriate C^N ligand. Time-dependent density functional theory investigations revealed that the dramatic and reversible color changes could be ascribed to a switch in the electronic distribution in the lowest excited state from bpyB2 to C^N. The stimulus-responsive iridium(III) complexes provide a prospective scaffold for future applications in color-tunable optical devices and chemosensing systems.

A Crystal Structure of an Oligoproline Hexamer with a Zig‐zag Arrangement

AbstractOligoprolines adopt the well‐defined polyproline II (PPII) helical conformation, even at a short chain length of six residues. These rigid peptides are versatile molecular rulers and scaffolds, yet there has been great difficulty in obtaining single crystals for X‐ray crystal structure analysis to probe their conformation in the solid state. Here, we report a crystal structure of an oligoproline hexamer bearing an N‐terminal terephthalic acid moiety. Comparison with that of a previously obtained crystal structure of a closely related hexaproline revealed influence of the terminal functional groups and the solvent on the crystal packing.

A plug-and-play system for polycyclic tetramate macrolactam production and functionalization

BackgroundThe biosynthesis of the natural product family of the polycyclic tetramate macrolactams (PoTeMs) employs an uncommon iterative polyketide synthase/non-ribosomal peptide synthetase (iPKS/NRPS). This machinery produces a universal PoTeM biosynthetic precursor that contains a tetramic acid moiety connected to two unsaturated polyene side chains. The enormous structural and hence functional diversity of PoTeMs is enabled by pathway-specific tailoring enzymes, particularly cyclization-catalyzing oxidases that process the polyene chains to form distinct ring systems, and further modifying enzymes.ResultsIkarugamycin is the first discovered PoTeM and is formed by the three enzymes IkaABC. Utilizing the iPKS/NRPS IkaA, we established a genetic plug-and-play system by screening eight different strong promoters downstream of ikaA to facilitate high-level heterologous expression of PoTeMs in different Streptomyces host systems. Furthermore, we applied the system on three different PoTeM modifying genes (ptmD, ikaD, and cftA), showing the general utility of this approach to study PoTeM post-PKS/NRPS processing of diverse tailoring enzymes.ConclusionBy employing our plug-and-play system for PoTeMs, we reconstructed the ikarugamycin biosynthesis and generated five derivatives of ikarugamycin. This platform will generally facilitate the investigation of new PoTeM biosynthetic cyclization and tailoring reactions in the future.

Semisynthesis of Glycosmis pentaphylla Alkaloid Derivatives: Pyranoacridone-Hydroxamic Acid Cytotoxic Conjugates with HDAC and Topoisomerase II α Dual Inhibitory Activity.

Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from Glycosmis pentaphylla des-N-methylacronycine (1) and noracronycine (8) pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an in vitro cytotoxicity assay, KT32 (10c) with noracronycine (8) as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC50 values of 1.0, 1.5, and 0.3 μM on MCF-7, CALU-3, and SCC-25 cell lines, respectively. KT32 (10c) showed potent HDAC inhibitory activity and partial Topo II α inhibitory activity in both enzyme assays. The SAR results strongly aligned with the predicted binding affinities from the molecular docking study. KT32 (10c) was further explored for a preliminary mechanistic understanding of SCC-25 cell lines. Flow cytometry analysis suggests that KT32 (10c) induces cell death through apoptosis, as evidenced by the substantial increase in the population of late apoptotic cells.

Guarding Drinking Water Safety against Harmful Algal Blooms: Could UV/Cl2 Treatment Be the Answer?

Frequent and severe occurrences of harmful algal blooms increasingly threaten human health by the release of microcystins (MCs). Urgent attention is directed toward managing MCs, as evidenced by rising HAB-related do not drink/do not boil advisories due to unsafe MC levels in drinking water. UV/chlorine treatment, in which UV light is applied simultaneously with chlorine, showed early promise for effectively degrading MC-LR to values below the World Health Organization's guideline limits. Still, much is unknown regarding potential disinfection byproduct formation and associated toxicity, which can occur from the reaction of chlorine and other reactive species with MCs and algal and natural organic matter. To ensure UV/chlorine guarding drinking water for human consumption, the degradation and detoxification of four of the most problematic MC variants, namely, MC-LR, -RR, -YR, and -LA, which differ in amino acid substituents, were evaluated using UV/chlorine and compared to results from chlorination. Overall, UV/chlorine effectively enhanced MC degradation kinetics and generated less halogenated disinfection byproducts in the target analysis of 11 types of DBPs_C1-3 from 7 classes, total organic chlorine, and nontarget analysis revealing 35 higher molecular weight DBPs_C46-52, which maintained the MC structures. Reactivity and cytotoxicity changes varied based on the individual amino acid moieties within the cyclic heptapeptide structure common to all MCs. Analogous trends in MC reactivity were observed in degradation kinetics and mixed MC competition reactions, aligning with individual amino acid structure-reactivity. Cytotoxicity results indicated no significant unintended toxic consequences from MC_DBPs. Our results suggest that UV/chlorine treatment offers an efficient strategy for treating MCs in drinking water.

Synergistic Antibacterial Action of Norfloxacin-Encapsulated G4 Hydrogels: The Role of Boronic Acid and Cyclodextrin.

In this present study, we developed and characterized a series of supramolecular G4 hydrogels by integrating β-cyclodextrin (β-CD) and boronic acid linkers into a supramolecular matrix to enhance antibacterial activity against Staphylococcus aureus (S. aureus). We systematically investigated how varying the number of free boronic acid moieties (ranging from two to six), along with guanosine and β-CD content, influences both the structural integrity and antimicrobial efficacy of these materials. Comprehensive characterization using FTIR, circular dichroism, X-ray diffraction, SEM, AFM, and rheological measurements confirmed successful synthesis and revealed that higher boronic acid content correlated with a stronger, more organized network. The most effective hydrogel displayed an inhibition zone of 25 mm in disk diffusion assays, and was further explored as a drug delivery platform, with the aim to exploit the capacity of the free β-CD cavity of the hydrogels to incorporate hydrophobic drugs. Norfloxacin (Nfx), a poorly water-soluble antibiotic, was successfully encapsulated within the hydrogel matrix through the inclusion of complex formation with β-CD, improving its solubility and enabling sustained, targeted release. The Nfx-loaded hydrogel expanded the inhibition zone to 49 mm and completely eradicated S. aureus cells within 24 h, outperforming both the unloaded hydrogel and free Nfx. These results highlight the synergistic effect of boronic acid moieties and controlled drug release, underlining the potential of these hydrogels as versatile platforms for localized antimicrobial therapy, such as in wound dressings or implant coatings. Nevertheless, further in vivo studies and long-term stability assessments are needed to fully establish clinical relevance, safety, and scalability before these systems can be translated into routine healthcare applications.

Maleimide grafting onto polysaccharides via mild condition esterification and its impact on their structure.

This study proposes an innovative approach to tailor the properties of two polysaccharides, microcrystalline cellulose (MCC) and potato starch, through chemical modification in dispersion. The methodology involves the grafting of 6-Maleimidohexanoic acid (6-MHA) moieties onto hydroxyl groups of the polysaccharides without dissolving them in order to keep their native structure preserved. To overcome the slow and inefficient reaction between carboxylic acids of 6-MHA and hydroxyl groups of the polysaccharides, a vinyl ester of 6-MHA was synthesized through the transvinylation of 6-MHA acid with vinyl acetate. The resulting 6-MHA ester was employed to introduce a new functionality to polysaccharides' hydroxyl groups via transesterification, catalyzed by potassium carbonate. To enhance the reactivity, the polysaccharides were mercerized prior to modification process. The efficiency of the transesterification reaction between the vinyl ester of 6-MHA and the hydroxyl groups of the polysaccharides was confirmed using Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance spectroscopy (NMR). Thermal behavior analysis was carried out using thermogravimetric analysis (TGA), while changes in crystallinity resulting from the modification were assessed through X-ray diffraction analysis (XRD). Finally, the impact of the modification on the morphology of polysaccharides was examined with environmental scanning electron microscopy (ESEM). Despite changes in microstructure, MCC kept its macrostructure remained morphologically unchanged while the granular structure of starch was damaged. Maleimide grafting onto MCC and starch has the potential to turn them into thermally reversible materials for various applications such as debondable adhesive or coating.

Advanced targeted curcumin delivery using biodegradable hierarchical microspheres with calcium pectinate matrix and hyaluronic acid moieties for enhancing colitis amelioration

Advanced targeted curcumin delivery using biodegradable hierarchical microspheres with calcium pectinate matrix and hyaluronic acid moieties for enhancing colitis amelioration

Multi-layer regulation of postprandial triglyceride metabolism in response to acute cold exposure.

Triglyceride-rich lipoproteins (TRLs) carry lipids in the bloodstream, where the fatty acid moieties are liberated by lipoprotein lipase (LPL) and taken up by peripheral tissues such as brown adipose tissue (BAT) and white adipose tissue (WAT), whereas the remaining cholesterol-rich remnant particles are cleared mainly by the liver. Elevated triglyceride (TG) levels and prolonged circulation of cholesterol-rich remnants are risk factors for cardiovascular diseases. Acute cold exposure decreases postprandial TG levels and is a potential therapeutic approach to treat hypertriglyceridemia. However, how acute cold exposure regulates TG metabolism remains incompletely understood. In the current study, we found that acute cold exposure simultaneously increases postprandial very-low-density lipoprotein (VLDL) production and TG clearance, with the latter playing a dominant role and resulting in decreased TG levels. Acute cold exposure increases LPL activity and TG uptake in BAT, while suppressing LPL activity and TG uptake in WAT. Mechanistically, acute cold exposure increases BAT LPL activity through transcriptional upregulation of Lpl and posttranscriptional regulation via inhibiting the hepatic insulin-ANGPTL8-ANGPTL3 axis, while suppressing WAT LPL activity through upregulation of ANGPTL4. Angptl8 knockout mice have dramatically decreased levels of circulating TG. In the absence of ANGPTL8, acute cold exposure increases rather than decreases circulating TG levels. Thus, our study reveals multi-layered regulation of acute cold response and postprandial TG metabolism, highlighting the key functions of ANGPTL3, 4, and 8 in response to acute cold exposure.