Remarkable enantioselectivity enhancement of the extractors with nonaxial chirality in liquid-liquid extraction of underivatized amino acids by introducing t-butyl group.

A class of carbonyl extractors, (R)-3, (R)-4, and (R)-5, with nonaxial chirality containing asymmetric carbons has been synthesized and studied for their efficiencies in enantioselective liquid-liquid extraction for underivatized amino acids. The bulky t-butyl ketone extractors, (R)-4 and (R)-5, showed the stereoselectivities ranging 5.4-9.4 of l/d ratio much better than those of the aldehyde extractor, (R)-3, ranging 2.4-5.2. The imine formation rates and yields of the t-butyl ketones were not significantly affected by their bulkiness and even in the absence of resonance-assisted hydrogen bond. This work confirms that a bulky t-butyl ketone can be a good choice in the development of an extractor not only with axial chirality but also with nonaxial chirality for the enantioselective extraction of unprotected amino acids.

Associations of tumor necrosis factor-α polymorphisms with the risk of asthma: a meta-analysis.

OBJECTIVE: Recently, potential correlations between tumor necrosis factor-α (TNF-α) polymorphisms and asthma were investigated by some pilot studies, but the results of these studies were inconsistent. Therefore, we performed this meta-analysis to better evaluate the relationship between TNF-α polymorphisms and the risk of asthma. METHODS: Eligible studies were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess correlations between TNF-α polymorphisms and asthma. RESULTS: A total of 50 studies were included for analyses. Significant associations with the risk of asthma were detected for TNF-α - 238 G/A, -308 G/A and - 857C/T polymorphisms in overall analyses. Further subgroup analyses according to ethnicity of participants revealed that TNF-α - 238 G/A polymorphism was significantly correlated with the risk of asthma in Caucasians, TNF-α - 308 G/A polymorphism was significantly correlated with the risk of asthma in West Asians, TNF-α - 857C/T polymorphism was significantly correlated with the risk of asthma in Caucasians, TNF-α - 863C/A polymorphism was significantly correlated with the risk of asthma in East Asians, and TNF-α - 1031 T/C polymorphism was significantly correlated with the risk of asthma in Caucasians and East Asians. CONCLUSIONS: Our findings indicated that TNF-α - 238 G/A, -308 G/A, -857C/T, -863C/A and - 1031 T/C polymorphisms may serve as potential biological markers for asthma in certain ethnicities.

A lectin-based diagnostic system using circulating antibodies to detect cervical intraepithelial neoplasia and cervical cancer.

In the present study, we developed serological strategies using immunoglobulin fractions obtained by protein A chromatography to screen for cervical cancer and cervical intraepithelial neoplasia I (CIN I). The reactivities of the immunoglobulins purified from sera of women with normal cytology, CIN I and cervical cancer were compared in enzyme-linked immunosorbent assays (ELISA) and enzyme-linked lectin assays (ELLAs). To capture the immunoglobulins, ELISAs and ELLAs were performed in protein A immobilized microplates. The reactivity of immunoglobulin in ELISA was in the increasing order normal cytology, CIN I and cervical cancer, while that in ELLAs for detecting fucosylation was in the decreasing order normal cytology, CIN I and cervical cancer. It was confirmed that women with CIN I were distinguishable from women with normal cytology or women with cervical cancer in the ELISA or the ELLA for detecting fucosylation with considerable sensitivity and specificity. Women with cervical cancer were also distinguishable from women with normal cytology with high sensitivity (ELISA: 97%, ELLA: 87%) and specificity (ELISA: 69%, ELLA: 72%). Moreover, the logistic regression model of the ELISA and the ELLA discriminated cervical cancer from normal cytology with 93% sensitivity and 93% specificity. These results indicate that the ELISAs and the ELLAs have great potential as strategies for primary screening of cervical cancer and CIN. It is expected that the ELISA and the ELLA can provide new insights to understand systemic changes of serum immunoglobulins during cervical cancer progression.

Increased sialylation and reduced fucosylation of exfoliated cervical cells are potential markers of carcinogenesis in the cervix.

BACKGROUND: The Pap test has been used for over 50 years for primary screening of cervical cancer. There has been no study of glycosylation changes in Pap test samples despite considerable potential of the glycosylation changes as biomarkers for detecting cancerous lesions. In this study, we developed a 96-well platform for enzyme-linked lectin assays (ELLAs) to evaluate glycosylation levels in cervical cells. METHODS: A total of 117 samples of exfoliated cervical cells (ECCs) from 37 individuals with normal cytology, 20 with cervical intraepithelial neoplasia (CIN) 1, 19 with CIN 2, 26 with CIN 3 and 15 with cervical cancer were analyzed by ELLAs. The wells of 96-well plates were coated with lysates of the cervical cells, and sialylation and fucosylation levels were compared between the groups. RESULTS: Sialylation levels increased and fucosylation levels decreased with increasing grade of cervical dysplasia. ELLAs for sialylation [ELLA-Sambucus nigra (SNAs)] and fucosylation [ELLA-Aleuria aurantia lectin (AAL)] discriminated not only CIN 2 and worse (CIN 2+: CIN 2, CIN 3, and cancer) from normal cytology but also CIN 3 and worse (CIN 3+: CIN3 and cancer) from normal cytology. ELLA-SNAs and ELLA-AALs distinguished cancer from normal cytology with a high true-positive rate (TPR) (ELLA-SNAs: 87%; ELLA-AALs: 87%) and low false-positive rate (FPR) (ELLA-SNAs: 19%; ELLA-AALs: 11%). CONCLUSIONS: The sialylation and fucosylation levels of ECCs as measured by ELLAs have great potential as biomarkers for primary screening of cervical cancer.

Preventive Role of Tetraspanin CD9 in Systemic Inflammation of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is frequently associated with extrapulmonary complications, including cardiovascular disease, diabetes, and osteoporosis. Persistent, low-grade, systemic inflammation underlies these comorbid disorders. Tetraspanins, which have a characteristic structure spanning the membrane four times, facilitate lateral organization of molecular complexes and thereby form tetraspanin-enriched microdomains that are distinct from lipid rafts. Recent basic research has suggested a preventive role of tetraspanin CD9 in COPD. CD9-enriched microdomains negatively regulate LPS-induced receptor formation by preventing CD14 from accumulating into the rafts, and decreased CD9 in macrophages enhances inflammation in mice. Mice doubly deficient in CD9 and a related tetraspanin, CD81, show pulmonary emphysema, weight loss, and osteopenia, a phenotype akin to human COPD. A therapeutic approach to up-regulating CD9 in macrophages might improve the clinical course of patients with COPD with comorbidities.

Deletion of tetraspanin CD9 diminishes lymphangiogenesis in vivo and in vitro.

Tetraspanins have emerged as key players in malignancy and inflammatory diseases, yet little is known about their roles in angiogenesis, and nothing is known about their involvement in lymphangiogenesis. We found here that tetraspanins are abundantly expressed in human lymphatic endothelial cells (LEC). After intrathoracic tumor implantation, metastasis to lymph nodes was diminished and accompanied by decreased angiogenesis and lymphangiogenesis in tetraspanin CD9-KO mice. Moreover, lymphangiomas induced in CD9-KO mice were less pronounced with decreased lymphangiogenesis compared with those in wild-type mice. Although mouse LEC isolated from CD9-KO mice showed normal adhesion, lymphangiogenesis was markedly impaired in several assays (migration, proliferation, and cable formation) in vitro and in the lymphatic ring assay ex vivo. Consistent with these findings in mouse LEC, knocking down CD9 in human LEC also produced decreased migration, proliferation, and cable formation. Immunoprecipitation analysis demonstrated that deletion of CD9 in LEC diminished formation of functional complexes between VEGF receptor-3 and integrins (α5 and α9). Therefore, knocking down CD9 in LEC attenuated VEGF receptor-3 signaling, as well as downstream signaling such as Erk and p38 upon VEGF-C stimulation. Finally, double deletion of CD9/CD81 in mice caused abnormal development of lymphatic vasculature in the trachea and diaphragm, suggesting that CD9 and a closely related tetraspanin CD81 coordinately play an essential role in physiological lymphangiogenesis. In conclusion, tetraspanin CD9 modulates molecular organization of integrins in LEC, thereby supporting several functions required for lymphangiogenesis.

Validation of noninvasive morphological and diffusion imaging in mouse emphysema by micro-computed tomography and hyperpolarized (129)Xe magnetic resonance imaging.

Animal disease models are pivotal in investigating the pathogenesis of emphysema and developing novel drugs, but the modalities to evaluate murine emphysema models have been of limited validity and sensitivity. In this study, we evaluated hyperpolarized (129)Xe magnetic resonance imaging (MRI) and micro-computed tomography (micro-CT) compared with traditional methods, such as plethysmography and histology. Elastase-treated mice and adiponectin knockout mice were used as murine emphysema models to evaluate these modalities. Three weeks after elastase administration, significant and heterogeneous emphysema was evaluated according to the mean linear intercept and plethysmography parameters. Notably, the distribution of low-density areas, as examined by micro-CT, correlated with the mean linear intercept and plethysmography parameters in whole lungs. These correlations were also observed in regional areas. Furthermore, we introduced hyperpolarized (129)Xe MRI, which can evaluate gas exchange between the alveoli and blood during spontaneous breathing. Parameters of gas exchange (fD) and alveolar size (Vs/Va) were significantly decreased in elastase-treated mice, and moderately correlated with the plethysmography parameters. Of importance, we could detect a decrease of the fD value in low-density areas with micro-CT, suggesting that gas exchange decreased in emphysematous lesions. Likewise, these parameters (fD and Vs/Va) were also decreased in adiponectin knockout mice, which exhibit emphysema with a homogeneous distribution. We demonstrated the feasibility of (129)Xe MRI and micro-CT in combination with traditional modalities. These noninvasive modalities provide complementary data that can be used for repeated estimations of regional gas exchange and lung morphology.

Tetraspanin CD151 protects against pulmonary fibrosis by maintaining epithelial integrity.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disorder of unknown etiology with few treatment options. Although tetraspanins are involved in various diseases, their roles in fibrosis have not been determined. OBJECTIVES: To investigate the role of tetraspanin CD151 in pulmonary fibrosis. METHODS: CD151 knockout (KO) mice were studied by histological, biochemical, and physiological analyses and compared with wild-type mice and CD9 KO mice. Further mechanistic analyses were performed in vitro, in vivo, and on samples from patients with IPF. MEASUREMENTS AND MAIN RESULTS: A microarray study identified an enrichment of genes involved in connective tissue disorders in the lungs of CD151 KO mice, but not in CD9 KO mice. Consistent with this, CD151 KO mice spontaneously exhibited age-related pulmonary fibrosis. Deletion of CD151 did not affect pulmonary fibroblast functions but instead degraded epithelial integrity via attenuated adhesion strength on the basement membrane; CD151-deleted alveolar epithelial cells exhibited increased α-SMA expression with activation of p-Smad2, leading to fibrotic changes in the lungs. This loss of epithelial integrity in CD151 KO lungs was further exacerbated by intratracheal bleomycin exposure, resulting in severe fibrosis with increased mortality. We also observed decreased numbers of CD151-positive alveolar epithelial cells in patients with IPF. CONCLUSIONS: CD151 is essential for normal function of alveolar epithelial cells; loss of CD151 causes pulmonary fibrosis as a result of epithelial disintegrity. Given that CD151 may protect against fibrosis, this protein represents a novel target for the treatment of fibrotic diseases.

Cold-Induced RNA-Binding Protein and RNA-Binding Motif Protein 3: Two RNA Molecular Chaperones Closely Related to Reproductive Development and Reproductive System Diseases.

Cold-induced RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) have recently been reported to be involved in cold stress in mammals. These proteins are expressed at low levels in various normal cells, tissues, and organs but can be upregulated upon stimulation by multiple stressors. Studies have shown that CIRP and RBM3 are multifunctional RNA molecular chaperones with different biological functions in various physiological and pathophysiological processes, such as reproductive development, the inflammatory response, the immune response, nerve injury regulation, and tumorigenesis. This paper reviews recent studies on the structure, localization and correlation of CIRP and RBM3 with reproductive development and reproductive system diseases.

The relationship between aquaporins and skin diseases.

Aquaporins (AQPs) are a family of transmembrane channel proteins that can rapidly transport water molecules. The main subtype expressed in the epidermis and dermis is AQP3. Studies have confirmed that AQPs exert certain physiological functions in the skin, such as the maintenance of normal shape, the regulation of body temperature, moisturization and hydration, anti-aging, damage repair and antigen presentation. The abnormal expression of AQPs in skin cells can lead to a variety of skin diseases. This review summarizes the relevance of AQPs in dermatophysiological and pathophysiological processes, highlighting their potential as new drug targets for the treatment of skin diseases.

Streptolysin S contributes to group A streptococcal translocation across an epithelial barrier.

Group A Streptococcus pyogenes (GAS) is a human pathogen that causes local suppurative infections and severe invasive diseases. Systemic dissemination of GAS is initiated by bacterial penetration of the epithelial barrier of the pharynx or damaged skin. To gain insight into the mechanism by which GAS penetrates the epithelial barrier, we sought to identify both bacterial and host factors involved in the process. Screening of a transposon mutant library of a clinical GAS isolate recovered from an invasive episode allowed identification of streptolysin S (SLS) as a novel factor that facilitates the translocation of GAS. Of note, the wild type strain efficiently translocated across the epithelial monolayer, accompanied by a decrease in transepithelial electrical resistance and cleavage of transmembrane junctional proteins, including occludin and E-cadherin. Loss of integrity of intercellular junctions was inhibited after infection with a deletion mutant of the sagA gene encoding SLS, as compared with those infected with the wild type strain. Interestingly, following GAS infection, calpain was recruited to the plasma membrane along with E-cadherin. Moreover, bacterial translocation and destabilization of the junctions were partially inhibited by a pharmacological calpain inhibitor or genetic interference with calpain. Our data indicate a potential function of SLS that facilitates GAS invasion into deeper tissues via degradation of epithelial intercellular junctions in concert with the host cysteine protease calpain.

Involvement of endothelial apoptosis underlying chronic obstructive pulmonary disease-like phenotype in adiponectin-null mice: implications for therapy.

RATIONALE: Chronic obstructive pulmonary disease is frequently complicated with comorbidities, such as cardiovascular disease, osteoporosis, and body weight loss, but the causal link remains unclear. OBJECTIVES: To investigate the role of adiponectin in the pathogenesis of chronic obstructive pulmonary disease and its potential use in therapy. METHODS: Adiponectin localization and dynamics in the lung were analyzed in an elastase-induced emphysema model. Next, the lung of adiponectin-knockout mice, extrapulmonary effects, and the underlying mechanism were investigated. Finally, we tested whether exogenous adiponectin could ameliorate the emphysematous change in adiponectin-knockout mice. MEASUREMENTS AND MAIN RESULTS: Adiponectin expression in lung vasculature and plasma concentration of adiponectin were reduced after elastase-instillation. Notably, adiponectin-knockout mice showed progressive alveolar enlargement and increased lung compliance. They further exhibited not only systemic inflammation, but also extrapulmonary phenotype, such as body weight loss, fat atrophy, and osteoporosis. Moreover, endothelial apoptosis was enhanced in the lungs of adiponectin-knockout mice, as evidenced by caspase-3 activity. Consistent with this, expressions of vascular endothelial growth factor receptor-2 and platelet endothelial cell adhesion molecule-1 on endothelial cells were decreased in the adiponectin-knockout mice. Finally, adenovirus-mediated adiponectin supplementation ameliorated the emphysematous phenotype. CONCLUSIONS: Adiponectin-knockout mice develop progressive chronic obstructive pulmonary disease-like phenotype with systemic inflammation and extrapulmonary phenotypes. Hypoadiponectinemia could thus play a critical role in the progression of chronic obstructive pulmonary disease and concomitant comorbidities through endothelial dysfunction. Together, adiponectin could be a novel target for chronic obstructive pulmonary disease therapy.

The composition of the carbon source and the time of cell harvest are critical determinants of the final yield of human papillomavirus type 16 L1 protein produced in Saccharomyces cerevisiae.

The L1 protein is a major component of prophylactic human papillomavirus (HPV) vaccines. Little effort has been made to improve the productivity of L1 protein by optimizing cell culture conditions although the high price of the vaccines is considered one of the factors limiting its widespread use. In biopharmaceutical manufacturing, strategies for optimizing culture conditions tend to focus on improvements in upstream processing rather than final yield because of the complexities of purification procedures. In this study, we investigated L1 protein productivity as a function of the composition of the carbon source and the point of cell harvesting in the Saccharomyces cerevisiae expression system. We performed 44 series of purifications and achieved the highest productivity when the cells were cultured in a medium composed of 7% glucose and 1% galactose for 144 h. The final yield of L1 protein was markedly affected by the glucose: galactose ratio and the point at which cells were harvested: there was a 15-fold difference between the lowest and highest yields. We believe that optimization of the composition of the carbon source and the time of cell harvest have considerable potential for reducing the cost of production of HPV L1 protein.

[Neuregulin promotes spermatogonia proliferation in mice].

OBJECTIVE: To explore the role of neuregulin (neural regulation of protein, NRG) in the process of mouse spermatogonia proliferation. METHODS: Mouse testis fragments were cultured in the medium DMEM containing purified NRG1beta or NRG3 at the concentration of 50, 100 and 200 ng/ml, respectively, followed by BrdU immunohistochemical staining and determination of the proliferation rate of spermatogonia. RESULTS: Compared with the control group, neuregulin significantly promoted the proliferation of spermatogonia (P < 0.05). The proliferation rates of spermatogonia cultured in the medium with 50, 100 and 200 ng/ml of NRG13 were 1.69, 1.55 and 1.86 times, and those with 50, 100 and 200 ng/ml of NRG3 were 1.35, 1.54 and 2.11 times that of the control. CONCLUSION: NRG1beta and NRG3 can promote the proliferation of mouse spermatogonia, and NRG is expected to be applied in the treatment of male infertility.

Detection of Budesonide and Other Anti-Inflammatory Drugs Based on Biological Nano Sensing Technology in the Treatment of Childhood Asthma.

Biological nano sensing technology is a new high-tech which is a cross fusion of biology, chemistry, physics, electronics and many other fields. Biological nano sensing technology mainly uses the unique chemical properties and corresponding physical properties of biomolecules at nanometer level to detect, which greatly improves the sensitivity and flexibility of detection. The micro effect, quantum effect and corresponding macro quantum tunneling effect of nano molecules make their corresponding nano biosensors have extremely high detection performance. In this paper, the antiinflammatory drugs such as budesonide, which are used to treat children's asthma, will be measured by the biological nano sensor based on the new nano materials. The treatment of children after the inhalation of budesonide and other drugs will be measured by the biological nano sensor technology. Finally, a new research idea will be provided for the research of children's asthma pathology and related fields. In this paper, in the actual preparation of nano sensors, we mainly use functionalized carbon nanotubes to prepare sensors. The main advantage is that the price is low and easy to market and experiment promotion.

Safinamide prevents lipopolysaccharide (LPS)-induced inflammation in macrophages by suppressing TLR4/NF-κB signaling.

Inflammation is a basal host defense response that eliminates the causes and consequences of infection and tissue injury. Macrophages are the primary immune cells involved in the inflammatory response. When activated by LPS, macrophages release various pro-inflammatory cytokines, chemokines, inflammatory mediators, and MMPs. However, unbridled inflammation causes further damage to tissues. Safinamide is a selective and reversible monoamine oxidase B (MAOB) inhibitor that has been used for the treatment of Parkinson's disease. In this study, we aimed to investigate whether safinamide has effects on LPS-treated macrophages. Our results show that safinamide inhibited the expression of pro-inflammatory cytokines such as IL-1α, TNF-α, and IL-6. Furthermore, safinamide suppressed the production of CXCL1 and CCL2, thereby preventing leukocyte migration. In addition, safinamide reduced iNOS-derived NO, COX-2-derived PGE2, MMP-2, and MMP-9. Importantly, the functions of safinamide mentioned above were found to be dependent on its inhibitory effect on the TLR4/NF-κB signaling pathway. Our data indicates that safinamide may exert a protective effect against inflammatory response.

Enantioselective extraction of unprotected amino acids coupled with racemization.

Scalable and economical methods for the production of optically pure amino acids, both natural and unnatural, are essential for their use as synthetic building blocks. Currently, enzymatic dynamic kinetic resolution (DKR) underpins some of the most effective processes. Here we report the development of enantioselective extraction coupled with racemization (EECR) for the chirality conversion of underivatized amino acids. In this process, the catalytic racemization of amino acids in a basic aqueous solution is coupled with the selective extraction of one enantiomer into an organic layer. Back-extraction from the organic layer to an acidic aqueous solution then completes the deracemization of the amino acid. The automation of the EECR process in a recycling flow reactor is also demonstrated. Continuous EECR is made possible by the sterically hindered chiral ketone extractant 5, which prevents the coextraction of the copper racemization catalyst because of its nonplanar geometry. Furthermore, the extractant 5 unexpectedly forms imines with amino acids faster and with greater enantioselectivity than less bulky derivatives, even though 5 cannot participate in intramolecular resonance-assisted hydrogen bonding. These features may allow EECR to challenge the preponderance of enzymatic DKR in the production of enantiomerically enriched amino acids.

Narciclasine attenuates LPS-induced acute lung injury in neonatal rats through suppressing inflammation and oxidative stress.

Acute lung injury (ALI) is a life-threatening disorder related to serious pulmonary inflammation. Narciclasine exhibits strong anti-inflammation activity and attenuates the reactive oxygen species (ROS) production. The present study aims to investigate the underlying mechanism related to the effect of narciclasine on the pathogenesis of neonatal acute lung injury (ALI). Narciclasine attenuated LPS-induced pathological injury and pulmonary edema. In addition, narciclasine suppressed the secretion of inflammatory cytokines, including necrosis factor-α (TNF-α), Interleukin (IL-6), IL-1ß, monocyte chemotactic protein-1 (MCP-1) in serum, and inhibited the expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in lung tissues of neonatal ALI rats. Furthermore, narciclasine alleviated oxidative stress and apoptosis in lung tissues. Importantly, narciclasine exerted an inhibition effect on NF-κB nuclear translocation and activation of Toll-like Receptor 4 (TLR4)/Nuclear factor (NF)-κB/Cyclooxygenase 2 (Cox2) signaling pathway. Taken together, narciclasine protected against lung injury via inhibition effect on excessive inflammation, oxidative stress and apoptosis, hence, narciclasine may be considered as an effective and novel agent for clinical therapeutic strategy of ALI Treatment.

The HA proteins of botulinum toxin disrupt intestinal epithelial intercellular junctions to increase toxin absorption.

The type B botulinum neurotoxin (BoNT) elicits flaccid paralysis and death in humans by intoxicating peripheral nerves after oral absorption. Here, we examine the function of the haemagglutinin (HA), a non-toxic component of the large 16S BoNT complex. We find that the HA acts in the intestine to disrupt epithelial barrier function by opening intercellular tight and adherens junctions. This allows transport of BoNT and other large solutes into the systemic circulation and explains how the type B BoNT complexes are efficiently absorbed. In vitro, HA appears to act on the epithelial cell via the basolateral membrane only, suggesting the possibility of another step in the absorptive process. These studies show that the 16S BoNT complex is a multifunctional protein assembly equipped with the machinery to efficiently breach the intestinal barrier and act systemically on peripheral nerves.

Hypertriglyceridemia in Watanabe heritable hyperlipidemic rabbits was associated with increased production and reduced catabolism of very-low-density lipoproteins.

Watanabe heritable hyperlipidemic (WHHL) rabbit is an animal model for human familial hypercholesterolemia. Recently, we segregated a new mutant of WHHL rabbits with plasma levels of triglycerides (TG) >500 mg/dl (designated as TGH-WHHL). To investigate the underlying mechanisms for hypertriglyceridemia, we compared TGH-WHHL with WHHL rabbits with lower plasma TG levels (<250 mg/dl, designated as TGL-WHHL). A Triton WR-1339 injection experiment revealed that TGH-WHHL rabbits had increased secretion and decreased clearance of TG-rich lipoproteins. Furthermore, TGH-WHHL rabbits had lower a post-heparin activity of lipoprotein lipase and a higher cholesterol ester transfer protein activity than TGL-WHHL rabbits. Cultured hepatocytes isolated from TGH-WHHL rabbits showed a higher secretion rate of TG and cholesterol than those of TGL-WHHL rabbits. In addition, TGH-WHHL rabbits exhibited marked insulin resistance. These data suggest that hypertriglyceridemia exhibited by WHHL rabbits is caused by both increased production and impaired catabolism of TG-rich lipoproteins and associated with insulin resistance.