Tumor Suppressor Adenomatous Polyposis Coli Sustains Dendritic Cell Tolerance through IL-10 in a ß-Catenin-Dependent Manner.

Dendritic cells (DC) play important roles in balancing immunity and tolerance, in which ß-catenin signaling plays an important role, yet the underlying mechanisms remain elusive. In this study, we investigated the functions of the tumor suppressor adenomatous polyposis coli (APC), also a key component of the ß-catenin upstream destruction complex in DC. APC depletion in DC does not alter DC and T cell homeostasis under resting conditions. However, APC deficiency in DC leads to attenuated antitumor immunity in mice, which exhibit fewer CD8+ T cells and more Foxp3+ regulatory T cells in tumor and draining lymph nodes. Loss of APC in DC does not affect the expression levels of costimulatory molecules. However, APC-deficient DC produce more IL-10 and exhibit a higher ability of inducing regulatory T cells but a lower ability of priming CD8+ T cells, both of which can be reversed by IL-10 inhibition. Lastly, ß-catenin depletion in APC-deficient DC rescues their antitumor immunity and reverses elevated IL-10 production. Taken together, our results identify that APC drives DC tolerance via the ß-catenin/IL-10 axis.

Ubc13 Promotes K63-Linked Polyubiquitination of NLRP3 to Activate Inflammasome.

NLRP3 inflammasome plays an important role in innate immune system through recognizing pathogenic microorganisms and danger-associated molecules. Deubiquitination of NLRP3 has been shown to be essential for its activation, yet the functions of Ubc13, the K63-linked specific ubiquitin-conjugating enzyme E2, in NLRP3 inflammasome activation are not known. In this study, we found that in mouse macrophages, Ubc13 knockdown or knockout dramatically impaired NLRP3 inflammasome activation. Catalytic activity is required for Ubc13 to control NLRP3 activation, and Ubc13 pharmacological inhibitor significantly attenuates NLRP3 inflammasome activation. Mechanistically, Ubc13 associates with NLRP3 and promotes its K63-linked polyubiquitination. Through mass spectrum and biochemical analysis, we identified lysine 565 and lysine 687 as theK63-linked polyubiquitination sites of NLRP3. Collectively, our data suggest that Ubc13 potentiates NLRP3 inflammasome activation via promoting site-specific K63-linked ubiquitination of NLRP3. Our study sheds light on mechanisms of NLRP3 inflammasome activation and identifies that targeting Ubc13 could be an effective therapeutic strategy for treating aberrant NLRP3 inflammasome activation-induced pathogenesis.

Molecular Basis of Artemisinin Derivatives Inhibition of Myeloid Differentiation Protein 2 by Combined in Silico and Experimental Study.

Artemisinin (also known as Qinghaosu), an active component of the Qinghao extract, is widely used as antimalarial drug. Previous studies reveal that artemisinin and its derivatives also have effective anti-inflammatory and immunomodulatory properties, but the direct molecular target remains unknown. Recently, several reports mentioned that myeloid differentiation factor 2 (MD-2, also known as lymphocyte antigen 96) may be the endogenous target of artemisinin in the inhibition of lipopolysaccharide signaling. However, the exact interaction between artemisinin and MD-2 is still not fully understood. Here, experimental and computational methods were employed to elucidate the relationship between the artemisinin and its inhibition mechanism. Experimental results showed that artemether exhibit higher anti-inflammatory activity performance than artemisinin and artesunate. Molecular docking results showed that artemisinin, artesunate, and artemether had similar binding poses, and all complexes remained stable throughout the whole molecular dynamics simulations, whereas the binding of artemisinin and its derivatives to MD-2 decreased the TLR4(Toll-Like Receptor 4)/MD-2 stability. Moreover, artemether exhibited lower binding energy as compared to artemisinin and artesunate, which is in good agreement with the experimental results. Leu61, Leu78, and Ile117 are indeed key residues that contribute to the binding free energy. Binding free energy analysis further confirmed that hydrophobic interactions were critical to maintain the binding mode of artemisinin and its derivatives with MD-2.

Molecular Mechanism of S1P Binding and Activation of the S1P1 Receptor.

Sphingosine-1-phosphate (S1P) is a lipidic mediator in mammals that functions either as a second messenger or as a ligand. In the latter case, it is transported by its HDL-associated apoM carrier and circulated in blood where it binds to specific S1P receptors on cell membranes and induces downstream reactions. Although S1P signaling pathways are essential for many biological processes, they are poorly understood at the molecular level. Here, the solved crystal structures of the S1P1 receptor were used to evaluate molecular dynamics (MD) simulations to generate greater detailed molecular insights into the mechanism of S1P signaling. The MD simulations provided observations at the coarse-grained and atomic levels indicating that S1P may access the receptor binding pocket directly from solvents. Lifting of the bulky N-terminal cap region of the receptor precedes initial S1P binding. Glu1213.29 guides S1P penetration, and together with Arg2927.34 is responsible for the stabilization of S1P in the binding pocket, which is consistent with experimental predictions. The complete binding of S1P is followed by receptor activation, wherein Trp2696.48 moves toward the transmembrane helix (TM) 7, resulting in the formation of an enhanced hydrogen bond network in the lower region of TM7. The distance between TM3 and TM6 is subsequently increased, resulting in the opening of the intracellular binding pocket that enables G protein binding. Further analysis of the force distribution network in the receptor yielded a detailed molecular understanding of the signal transmission network that is activated upon agonist binding.

Dissecting the Innate Immune Recognition of Opioid Inactive Isomer (+)-Naltrexone Derived Toll-like Receptor 4 (TLR4) Antagonists.

The opioid inactive isomer (+)-naltrexone is one of the rare Toll-like receptor 4 (TLR4) antagonists with good blood-brain barrier (BBB) permeability, which is a lead with promising potential for treating neuropathic pain and drug addiction. (+)-Naltrexone targets the lipopolysaccharides (LPS) binding pocket of myeloid differentiation protein 2 (MD-2) and blocks innate immune TLR4 signaling. However, the details of the molecular interactions of (+)-naltrexone and its derivatives with MD-2 are not fully understood, which hinders the ligand-based drug discovery. Herein, in silico and in vitro assays were performed to elucidate the innate immune recognition of the opioid inactive (+)-isomers. The results showed that the conserved LPS binding pocket of MD-2 accommodated these opioid inactive (+)-isomers. The calculated binding free energies of (+)-naltrexone and its derivatives in complex with MD-2 correlated well with their experimental binding affinities and TLR4 antagonistic activities. Hydrophobic residues in the MD-2 cavity interacted directly with these (+)-naltrexone based TLR4 antagonists and principally participated in ligand binding. Increasing the hydrophobicity of substituted group at N-17 improved its TLR4 antagonistic activity, while charged groups disfavored the binding with MD-2. Molecular dynamics (MD) simulations showed the binding of (+)-naltrexone or its derivatives to MD-2 stabilized the "collapsed" conformation of MD-2, consequently blocking the binding and signaling of TLR4. Thermodynamics and dynamic analysis showed the topology of substituted group at N-17 of (+)-naltrexone affected the binding with MD-2 and TLR4 antagonistic activity. This study provides a molecular insight into the innate immune recognition of opioid inactive (+)-isomers, which would be of great help for the development of next-generation of (+)-opioid based TLR4 antagonists.

Enzymo-chemical preparation, physico-chemical characterization and hypolipidemic activity of granular corn bran dietary fibre.

Corn bran dietary fibre (CF) was paid more attention for its anticancer and hypolipidemic activities. In this paper, corn bran was firstly decomposed to the threadlike fibre (CF1) by multiple enzymes and then further modified to the granular fibre (CF2) by alkali under high pressure and high temperature (APT). The two types of fibres were characterized by scanning electron microscope (SEM) and near-infrared spectrophotometer (IR), and investigated by hydration measurements and nitrite adsorption assays. The results showed that CF2 had more much specific surface area, and displayed 4.7, 6.3 and 30-fold increases in water retention (WR), swelling capacity (SC) and nitrite absorption (NA), compared with CF1, respectively. The rat feeding trials showed that the granular fibre could decrease total cholesterol (TC), triglyceride (TG) and low density lipoprotein-cholesterol (LDLC) by 41.4 %, 20.7 % and 56.5 %, respectively. These excellent physiological activities indicate that CF2 will be a potentially available dietary ingredient in functional food industries, and meanwile imply that the enzymochemical method is a desired strategy for CF processing.

Mucus adhesion vs. mucus penetration? Screening nanomaterials for nasal inhalation by MD simulation.

Nanocarrier-aided drug delivery techniques have improved the absorption and permeability of drugs in nose-to-brain delivery. However, the molecular properties of nanocarriers during the delivery process are of great interest; in particular, the characteristics when penetrating barriers in vivo are crucial for the screening and optimization of materials for nasal inhalation. In this study, we have focused on two types of delivery systems: mucoadhesive nanoparticles (MAPs) and mucopenetrating nanoparticles (MPPs); both have been widely used for mucosal delivery, although a method for selecting the more effective type of drug carriers for mucosal delivery has not been established. Molecular dynamics (MD) simulations were used to reveal the all-atom dynamic characteristics of the interaction between different delivery systems and the nasal mucus protein MUC5AC. Among the systems tested, hydroxypropyltrimethyl ammonium chloride chitosan (HTCC) had the strongest interaction with mucin, suggesting it had better mucoadhesive performance, and that it interacted with MUC5AC more strongly than unmodified chitosan. In contrast, the mucus-penetrating material polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA), had almost no interaction with MUC5AC. The results of the MD simulations were verified by in vitro experiments on nanoparticles (NPs) and mucin binding. The drug delivery performance of the four types of NPs, analyzed by in vitro and ex vivo mucosal penetration, were all generally consistent with the properties of the material predicted from the MD simulation. These clues to the molecular mechanism of MAPs and MPPs may provide useful insight into the screening and optimization of nanomaterials suitable for nasal inhalation.

Nanoscale cutting using self-excited microcantilever.

The application of self-excitation is proposed to improve the efficiency of the nanoscale cutting procedure based on use of a microcantilever in atomic force microscopy. The microcantilever shape is redesigned so that it can be used to produce vibration amplitudes with sufficient magnitudes to enable the excitation force applied by an actuator to be transferred efficiently to the tip of the microcantilever for the cutting process. A diamond abrasive that is set on the tip is also fabricated using a focused ion beam technique to improve the cutting effect. The natural frequency of the microcantilever is modulated based on the pressing load. Under conventional external excitation conditions, to maintain the microcantilever in its resonant state, it is necessary to vary the excitation frequency in accordance with the modulation. In this study, rather than using external excitation, the self-excitation cutting method is proposed to overcome this difficulty. The self-excited oscillation is produced by appropriate setting of the phase difference between the deflection signal of the microcantilever and the feedback signal for the actuator. In addition, it is demonstrated experimentally that the change in the phase difference enables us to control the amplitude of the self-excitation. As a result, control of the cutting depth is achieved via changes in the phase difference.

Origin, genetic diversity, adaptive evolution and transmission dynamics of Getah virus.

As a member of the Alphavirus, Getah virus (GETV) was becoming more serious and posing a serious threat to animal safety and public health. However, the circulation, distribution and evolution of GETV is not well understood. Hence, we integrated a variety of bioinformatic methodologies, from genomic alterations to systematic analysis, phylogeography, selection, adaptive analysis, prediction of protein modification, structural biology and molecular dynamics simulations to understand the characteristics of GETV. The results of phylogeography and molecular evolution show that due to the lack of vaccine, GETV is rapidly expanding its host range and geographical distribution at a high evolutionary rate. We also predicted the important modification sites, and identified the adaptive and active selection sites. Finally, the analysis of spatial structure and function showed that six adaptive sites may be related to the structural stability, receptor binding ability, immunogenicity and immune evasion of the virus, respectively. The data from this study have important implications for the understanding of ongoing GETV outbreaks worldwide and will guide future efforts to develop effective preventive and control measures against GETV. In particular, biosafety measures should be strengthened immediately to prevent GETV from becoming a pandemic, especially in China, South Korea and Japan.

Vps33B controls Treg cell suppressive function through inhibiting lysosomal nutrient sensing complex-mediated mTORC1 activation.

The suppressive function of regulatory T (Treg) cells is tightly controlled by nutrient-fueled mechanistic target of rapamycin complex 1 (mTORC1) activation, yet its dynamics and negative regulation remain unclear. Here we show that Treg-specific depletion of vacuolar protein sorting 33B (Vps33B) in mice results in defective Treg cell suppressive function and acquisition of effector phenotype, which in turn leads to disturbed T cell homeostasis and boosted antitumor immunity. Mechanistically, Vps33B binds with lysosomal nutrient-sensing complex (LYNUS) and promotes late endosome and lysosome fusion and clearance of the LYNUS-containing late endosome/lysosome, and therefore suppresses mTORC1 activation. Vps33B deficiency in Treg cells results in disordered endosome lysosome fusion, which leads to accumulation of LYNUS that causes elevated mTORC1 activation and hyper-glycolytic metabolism. Taken together, our study reveals that Vps33B maintains Treg cell suppressive function through sustaining endolysosomal homeostasis and therefore restricting amino acid-licensed mTORC1 activation and metabolism.

SIRT3-mediated deacetylation of NLRC4 promotes inflammasome activation.

Salmonella typhimurium (S. typhimurium) infection of macrophage induces NLRC4 inflammasome-mediated production of the pro-inflammatory cytokines IL-1ß. Post-translational modifications on NLRC4 are critical for its activation. Sirtuin3 (SIRT3) is the most thoroughly studied mitochondrial nicotinamide adenine dinucleotide (NAD+) -dependent deacetylase. We wondered whether SIRT3 mediated-deacetylation could take part in NLRC4 inflammasome activation. Methods: We initially tested IL-1ß production and pyroptosis after cytosolic transfection of flagellin or S. typhimurium infection in wild type and SIRT3-deficient primary peritoneal macrophages via immunoblotting and ELISA assay. These results were confirmed in SIRT3-deficient immortalized bone marrow derived macrophages (iBMDMs) which were generated by CRISPR-Cas9 technology. In addition, in vivo experiments were conducted to confirm the role of SIRT3 in S. typhimurium-induced cytokines production. Then NLRC4 assembly was analyzed by immune-fluorescence assay and ASC oligomerization assay. Immunoblotting, ELISA and flow cytometry were performed to clarify the role of SIRT3 in NLRP3 and AIM2 inflammasomes activation. To further investigate the mechanism of SIRT3 in NLRC4 activation, co-immunoprecipitation (Co-IP), we did immunoblot, cellular fractionation and in-vitro deacetylation assay. Finally, to clarify the acetylation sites of NLRC4, we performed liquid chromatography-mass spectrometry (LC-MS) and immunoblotting analysis. Results: SIRT3 deficiency led to significantly impaired NLRC4 inflammasome activation and pyroptosis both in vitro and in vivo. Furthermore, SIRT3 promotes NLRC4 inflammasome assembly by inducing more ASC speck formation and ASC oligomerization. However, SIRT3 is dispensable for NLRP3 and AIM2 inflammasome activation. Moreover, SIRT3 interacts with and deacetylates NLRC4 to promote its activation. Finally, we proved that deacetylation of NLRC4 at Lys71 or Lys272 could promote its activation. Conclusions: Our study reveals that SIRT3 mediated-deacetylation of NLRC4 is pivotal for NLRC4 activation and the acetylation switch of NLRC4 may aid the clearance of S. typhimurium infection.

Curvature effect and stabilize ruptured membrane of BAX derived peptide studied by molecular dynamics simulations.

BAX protein plays a key role in mitochondrial membrane permeabilization and cytochrome c release upon apoptosis. The C-terminal transmembrane domain (TMD) of BAX is supposed to act a membrane anchor when BAX is activated leading to programmed cell death. Previous studies indicate that the C-terminal transmembrane domain of BAX mediates membrane disruption and pore formation, however, the mechanism of the membrane disruption and pore-forming capability of BAX C-terminal transmembrane domain still unclear. Here, we performed all-atom (AA) molecular dynamics simulations to study the membrane effect of TMD peptide. We also conducted coarse-grained (CG) molecular dynamics simulations to study the membrane curvature and the stabilization of ruptured membrane pores effect of TMD peptides. Our results indicated that TMD peptide decreases the local POPC lipids order. The membrane binding of TMD induced a positive membrane curvature, moreover, certain numbers of TMD could stabilize ruptured membrane pore in both CG and AA simulations. These results provide insight into the structure details of membrane pore formation by TMD peptides. The diameters of the pore are qualitatively in good agreement with available experimental data.

Environment-friendly determination of low concentration azobenzene beta-cyclodextrin-modified electrode.

OBJECTIVE: To study environment-friendly determination of azobenzene in trace amounts using beta-cyclodextrin (beta-CD)-modified Au electrode. METHODS: beta-CD-modified Au electrode was fabricated with a two-step approach, and then a gold electrode modified with beta-CD was used to detect azobenzene by employing Osteryoung square wave voltammetry. RESULTS: The modified electrode could detect azobenzene, showing a good linearity between the electrochemical current and concentration. CONCLUSION: Although the electrochemical current is related with concentration, the detection limit is around 1.0 x 10(-10) mol/L. This study may provide a new environment-friendly approach for monitoring water quality.

Association of body mass index, waist circumference, and metabolic syndrome with serum cystatin C in a Chinese population.

BACKGROUND: The aim of the study was to evaluate the association of body mass index (BMI), waist circumference (WC), and metabolic syndrome (MetS) with serum cystatin C (CysC) in a Chinese population. METHODS: The population was composed of 5866 subjects. MetS was diagnosed using the American Heart Association/National Heart, Lung, and Blood Institute 2005 (NCEP-R) criteria. Covariates were analyzed using logistic regression and Spearman partial correlation. RESULTS: In this population, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), high sensitivity C-reactive protein (hs-CRP), BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine (Scr), and CysC were significantly higher, and HDL-C and the estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) (eGFRCKD-EPI) were significantly lower in the MetS than in the non-MetS group. TG, LDL-C, FPG, hs-CRP, BMI, WC, SBP, DBP, and Scr were significantly higher, and HDL-C and eGFRCKD-EPI were significantly lower in the 4th quartile than in the 1st quartile of CysC. Logistic regression analysis showed that sex, age, hs-CRP, and CysC were independently associated with the presence of MetS (OR = 3.732, 1.028, 1.051, and 3.334, respectively; P < 0.05). No significant association between the presence of MetS and either Scr or eGFRCKD-EPI was observed. After adjustment for age and sex, BMI, WC, hs-CRP, and Scr were all positively correlated, whereas eGFRCKD-EPI was negatively correlated with CysC (r = 0.029, 0.061, 0.189, 0.227, and -0.210, respectively; P < 0.05). CONCLUSION: The present study revealed that the CysC was more closely associated with the presence of MetS, as compared Scr or eGFRCKD-EPI. CysC was positively correlated with BMI, and more strongly, positively correlated with WC and inflammation.

Allostery in BAX protein activation.

BAX is a member of the proapoptotic BCL-2 family of proteins, which is involved in the regulation of the intrinsic pathway of apoptosis. In the process of apoptosis, BH3-only molecules activate cytosolic BAX. Activated BAX molecules insert into the mitochondrial outer membrane with their [Formula: see text]-helix and form oligomers that lead to membrane poration, resulting in the release of apoptogenic factors including cytochrome c. Recently, a novel interaction site for the binding of the BIM SAHB ligand to BAX was reported. BIM SAHB binding was shown to invoke the exposure of the 6A7 epitope (amino acids 13-19) and of the BH3 domain of BAX, followed by mobilization of the BAX [Formula: see text]-helix. However, the intramolecular pathway for signal transmission in BAX, from BIM SAHB binding to mobilization of the [Formula: see text]-helix largely remained elusive. For a molecular understanding of the activation of BAX, and thus the first steps in apoptosis, we performed microsecond atomistic molecular dynamics simulations both of the BAX protein and of the BAX:BIM SAHB complex in aqueous solution. In agreement with experiment, the 6A7 and BH3 domains adopt a more solvent-exposed conformation within the BAX:BIM SAHB complex. BIM SAHB binding was found to stabilize the secondary structure of the [Formula: see text]9-helix. A force distribution analysis revealed a force network of residue-residue interactions responsible for signal transmission from the BIM SAHB binding site predominantly via the [Formula: see text]4- and [Formula: see text]6-helices to the [Formula: see text]9-helix on the opposite site of the protein.

Binding Characteristics of Sphingosine-1-Phosphate to ApoM hints to Assisted Release Mechanism via the ApoM Calyx-Opening.

Sphingosine-1-phosphate (S1P) is a lysophospholipid mediator carried by the HDL-associated apoM protein in blood, regulating many physiological processes by activating the G protein-coupled S1P receptor in mammals. Despite the solved crystal structure of the apoM-S1P complex, the mechanism of S1P release from apoM as a part of the S1P pathway is unknown. Here, the dynamics of the wild type apoM-S1P complex as well as of mutants were investigated by means of atomistic molecular dynamics simulations. The potential of mean force for S1P unbinding from apoM reflected a large binding strength of more than 60 kJ/mol. This high unbinding free energy for S1P underlines the observed specificity of the physiological effects of S1P as it suggests that the spontaneous release of S1P from apoM is unlikely. Instead, S1P release and thus the control of this bioactive lipid probably requires the tight interaction with other molecules, e.g. with the S1P receptor. Mutations of specific S1P anchoring residues of apoM decreased the energetic barrier by up to 20 kJ/mol. Moreover, the ligand-free apoM protein is shown to adopt a more open upper hydrophilic binding pocket and to result in complete closure of the lower hydrophobic cavity, suggesting a mechanism for adjusting the gate for ligand access.

A Critical Comparison of Biomembrane Force Fields: Structure and Dynamics of Model DMPC, POPC, and POPE Bilayers.

Atomistic molecular dynamics simulations have become an important source of information for the structure and dynamics of biomembranes at molecular detail difficult to access in experiments. A number of force fields for lipid membrane simulations have been derived in the past; the choice of the most suitable force field is, however, frequently hampered by the availability of parameters for specific lipids. Additionally, the comparison of different quantities among force fields is often aggravated by varying simulation parameters. Here, we compare four atomistic lipid force fields, namely, the united-atom GROMOS54a7 and the all-atom force fields CHARMM36, Slipids, and Lipid14, for a broad range of structural and dynamical properties of saturated and monounsaturated phosphatidylcholine bilayers (DMPC and POPC) as well as for monounsaturated phosphatidylethanolamine bilayers (POPE). Additionally, the ability of the different force fields to describe the gel-liquid crystalline phase transition is compared and their computational efficiency estimated. Moreover, membrane properties like the water flux across the lipid bilayer and lipid acyl chain protrusion probabilities are compared.

Association between Insulin Resistance, Metabolic Syndrome and Nonalcoholic Fatty Liver Disease in Chinese Adults.

BACKGROUND: The aim of this study was to assess the association between insulin resistance, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in Chinese adults. METHODS: Fifty five subjects with NAFLD and 55 controls were enrolled for the study. Waist circumference, blood pressure, plasma triglyceride, high density lipoprotein cholesterol and fasting plasma glucose concentrations and homeostasis model assessment of insulin resistance (HOMA-IR) values as an index used to quantify insulin resistance were measured and analyzed. Logistic regression was analyzed to predict independent risk factors of NAFLD. RESULTS: The prevalence of metabolic syndrome in NAFLD group was obviously higher than in controls group (47.3% VS 3.6%, P<0.001). There were all significant differences of each component of metabolic syndrome and HOMA-IR values in comparison of nonalcoholic fatty liver disease (NAFLD) and controls group. In a logistic regression analysis, age, diastolic blood pressure, waist circumference and HOMA-IR were the covariates independently associated with the presence of NAFLD (Odds Ratio=1.107, 1.083, 1.218 and 16.836; 95% CI: 1.011∼1.211, 1.001∼1.173, 1.083∼1.370 and 3.626∼78.168, respectively; P<0.05) CONCLUSION: NAFLD was closely associated with metabolic syndrome and insulin resistance was a very strong predictor of NAFLD.

Association of the apolipoprotein B/apolipoprotein A-I ratio and low-density lipoprotein cholesterol with insulin resistance in a Chinese population with abdominal obesity.

The aim of this study is to assess the relationships among the apolipoprotein B/apolipoprotein A-I ratio (apoB/apoA-I ratio), low-density lipoprotein cholesterol (LDL-C) and insulin resistance (IR) in a Chinese population with abdominal obesity. This is a population-based, cross-sectional study of 3,945 men and 2,141 women with abdominal obesity. Individuals were referred to a primary health service and recruited for analysis. IR was measured using a homeostasis model assessment of insulin resistance (HOMA2-IR) with a HOMA2 calculator. Metabolic syndrome (MetS) was diagnosed using International Diabetes Federation (IDF) criteria. Comparing the apoB/apoA-I ratio and lipid indices using the HOMA2-IR showed that the ratio, LDL-C, total cholesterol level (TC) and triglyceride level (TG) were higher; and the high-density lipoprotein cholesterol level (HDL-C) was lower in the fourth than in the first quartile in both sexes (p ≤ 0.001). After adjustment for age, HOMA2-IR was positively correlated with the apoB/apoA-I ratio, LDL-C, TC and TG; and negatively correlated with HDL-C in men (all p < 0.0001). HOMA2-IR was also positively correlated with the apoB/apoA-I ratio, LDL-C, TC and TG; and negatively correlated with HDL-C in women (all p < 0.01). After adjustment for age and LDL-C, HOMA2-IR was found to be correlated with the apoB/apoA-I ratio in both men and women (r = 0.066 and 0.116, p < 0.0001). After adjustment for age and the apoB/apoA-I ratio, HOMA2-IR was correlated with LDL-C in men and women (r = 0.063 and 0.044, p < 0.0001 and p = 0.0431, respectively). Gender, age, LDL-C, BMI, HOMA2-IR and apoB/apoA-I were the covariates independently associated with presence of the MetS (Odds ratio, OR: 2.183, 1.034, 1.013, 1.157, 1.726 and 1.570, respectively; all p < 0.05). In conclusion, the study showed that the apoB/apoA-I ratio and LDL-C were positively correlated with IR. Excluding reciprocal interactions, the apoB/apoA-I ratio and LDL-C were still significantly correlated with IR, but the apoB/apoA-I ratio showed a greater correlation with IR than LDL-C in women with abdominal obesity, compared with men with abdominal obesity. Both LDL-C and apoB/apoA-I were independent risk factors of MetS, and the apoB/apoA-I ratio was stronger in this regard than LDL-C for this obese population.