Obese Mice with Dyslipidemia Exhibit Meibomian Gland Hypertrophy and Alterations in Meibum Composition and Aqueous Tear Production.

BACKGROUND: Dyslipidemia may be linked to meibomian gland dysfunction (MGD) and altered meibum lipid composition. The purpose was to determine if plasma and meibum cholesteryl esters (CE), triglycerides (TG), ceramides (Cer) and sphingomyelins (SM) change in a mouse model of diet-induced obesity where mice develop dyslipidemia. METHODS: Male C57/BL6 mice (8/group, age = 6 wks) were fed a normal (ND; 15% kcal fat) or an obesogenic high-fat diet (HFD; 42% kcal fat) for 10 wks. Tear production was measured and meibography was performed. Body and epididymal adipose tissue (eAT) weights were determined. Nano-ESI-MS/MS and LC-ESI-MS/MS were used to detect CE, TG, Cer and SM species. Data were analyzed by principal component analysis, Pearson's correlation and unpaired t-tests adjusted for multiple comparisons; significance set at p ≤ 0.05. RESULTS: Compared to ND mice, HFD mice gained more weight and showed heavier eAT and dyslipidemia with higher levels of plasma CE, TG, Cer and SM. HFD mice had hypertrophic meibomian glands, increased levels of lipid species acylated by saturated fatty acids in plasma and meibum and excessive tear production. CONCLUSIONS: The majority of meibum lipid species with saturated fatty acids increased with HFD feeding with evidence of meibomian gland hypertrophy and excessive tearing. The dyslipidemia is associated with altered meibum composition, a key feature of MGD.

The relationship between phospholipids and insulin resistance: From clinical to experimental studies.

Insulin resistance induced by high-fat diet and impropriate life style is a major contributor to the pathogenesis of metabolic disease. However, the underlying molecular mechanisms remain unclear. Recent studies in metabolic dysfunction have extended this beyond simply elevated cholesterol and triglycerides levels and have identified a key role for lipid metabolism. For example, altered phospholipid metabolism has now become central in the pathogenesis of metabolic disease. In this review, we discuss the association between insulin sensitivity and phospholipid metabolism and highlight the most significant discoveries generated over the last several decades. Finally, we summarize the current knowledge surrounding the molecular mechanisms related to phospholipids and insulin resistance and provide new insight for future research into their relationship.

Profiling of lipid species by normal-phase liquid chromatography, nanoelectrospray ionization, and ion trap-orbitrap mass spectrometry.

Detailed analysis of lipid species can be challenging due to their structural diversity and wide concentration range in cells, tissues, and biofluids. To address these analytical challenges, we devised a reproducible, sensitive, and integrated lipidomics workflow based on normal-phase liquid chromatography-Fourier transform mass spectrometry (LC-FTMS) and LC-ITMS(2) (ion trap tandem mass spectrometry) for profiling and structural analysis of lipid species. The workflow uses a normal-phase LC system for efficient separation of apolar and polar lipid species combined with sensitive and specific analysis powered by a chip-based nanoelectrospray ion source and a hybrid ion trap-orbitrap mass spectrometer. The workflow was executed using a primary LC-FTMS survey routine for identification and profiling of lipid species based on high-mass accuracy and retention time followed by a targeted LC-ITMS(2) routine for characterizing the fatty acid moieties of identified lipid species. We benchmarked the performance of the workflow by characterizing the chromatographic properties of the LC-MS system for general lipid analysis. In addition, we demonstrate the efficacy of the workflow by reporting a study of low-abundant triacylglycerol and ceramide species in mouse brain cerebellum and 3T3-L1 adipocytes, respectively. The workflow described here is generic and can be extended for detailed lipid analysis of sample matrices having a wide range of lipid compositions.

Lipoprotein subclass profiles in young adults born preterm at very low birth weight.

BACKGROUND: Adults born preterm at very low birth weight (VLBW ≤ 1500g) have increased risk factors for cardiovascular diseases including high blood pressure and impaired glucose regulation. Non-optimal lipoprotein profile is generally also likely to affect the increased cardiovascular risk, but lipoprotein subclass level data on adults born at VLBW are sparse. SUBJECTS AND METHODS: We studied 162 subjects born at VLBW and 169 term-born controls, aged 19 to 27 years. Total lipid, triglyceride and cholesterol concentrations of 14 lipoprotein subclasses were determined by proton nuclear magnetic resonance spectroscopy in the fasting state and in 2-hour serum samples from an oral glucose tolerance test. FINDINGS: In comparison to controls, VLBW subjects had significantly higher fasting concentration of triglycerides in chylomicrons and largest very-low-density lipoprotein particles [XXL-VLDL-TG, difference 0.026 (95% CI: 0.004 to 0.049), P=0.024], and of triglycerides in small high-density lipoprotein particles [S-HDL-TG, 0.026 (95% CI: 0.002 to 0.051), P=0.037]. The seemingly important role of triglycerides was further supported by principal component analysis in which the first component was characterized by multiple lipoprotein triglyceride measures. CONCLUSIONS: Young adults born at VLBW and their peers born at term had triglyceride-related differences in both VLDL and HDL subclasses. These differences suggest that the increased risk factors for cardiovascular diseases among the VLBW individuals in adulthood may partly relate to impaired triglyceride metabolism.

[Body mass index influence on aortic valve stenosis]. / Wskaznik masy ciala, a naturalny przebieg zwezenia lewego ujscia tetniczego.

AIM: The 12 months' observation of body mass index (BMI) influence on natural course of aortic valve stenosis (AVS). PATIENTS: 60 AVS patients who did not agree for operational treatment were divided into group A (n = 15) with BMI 20-25, group B (n = 27) with BMI 25,01-30 and group C BMI > 30. METHODS: Plasma Lp(a), total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha) as well as titers of immunoglobulin (Ig) class G, A, M against chlamydia pneumoniae were measured every 12 months. Echo-cardiographic evaluation of aortic valve was also done every 12 months. RESULTS: Means serum CRP at 12 month was the highest in group C. No differences in mean serum TNF-alpha and IL-6 levels as well as in Ig titers between groups A, B, C were found. At 12 month of observation HDL/total cholesterol ratio as well as HDL/LDL-cholesterol ratio were the lowest in group B. Left atrium diameter and right ventricle diameter were bigger in groups B and C compared to group A at the visit I and after 12 months of observation. Systolic intraventricular septum (IVS syst) thickness was the highest in group C at visit I. Diastolic left ventricle posterior wall thickness (LVPW) was the highest in group C during 12 months of observation. CONCLUSION: The increase in fat tissue mass may lead to increase in inflammatory process and cardiac muscle remodeling in AVS patients.

Human adipocyte differentiation and composition of disease-relevant lipids are regulated by miR-221-3p.

MicroRNA-221-3p (miR-221-3p) is associated with both metabolic diseases and cancers. However, its role in terminal adipocyte differentiation and lipid metabolism are uncharacterized. miR-221-3p or its inhibitor was transfected into differentiating or mature human adipocytes. Triglyceride (TG) content and adipogenic gene expression were monitored, global lipidome analysis was carried out, and mechanisms underlying the effects of miR-221-3p were investigated. Finally, cross-talk between miR-221-3p expressing adipocytes and MCF-7 breast carcinoma (BC) cells was studied, and miR-221-3p expression in tumor-proximal adipose biopsies from BC patients analyzed. miR-221-3p overexpression inhibited terminal differentiation of adipocytes, as judged from reduced TG storage and gene expression of the adipogenic markers SCD1, GLUT4, FAS, DGAT1/2, AP2, ATGL and AdipoQ, whereas the miR-221-3p inhibitor increased TG storage. Knockdown of the predicted miR-221-3p target, 14-3-3γ, had similar antiadipogenic effects as miR-221-3p overexpression, indicating it as a potential mediator of mir-221-3p function. Importantly, miR-221-3p overexpression inhibited de novo lipogenesis but increased the concentrations of ceramides and sphingomyelins, while reducing diacylglycerols, concomitant with suppression of sphingomyelin phosphodiesterase, ATP citrate lyase, and acid ceramidase. miR-221-3p expression was elevated in tumor proximal adipose tissue from patients with invasive BC. Conditioned medium of miR-221-3p overexpressing adipocytes stimulated the invasion and proliferation of BC cells, while medium of the BC cells enhanced miR-221-3p expression in adipocytes. Elevated miR-221-3p impairs adipocyte lipid storage and differentiation, and modifies their ceramide, sphingomyelin, and diacylglycerol content. These alterations are relevant for metabolic diseases but may also affect cancer progression.

A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy.

PURPOSE: To conduct the first randomized trial on classical and medium-chain triglyceride (MCT) versions of the ketogenic diet, examining efficacy and tolerability after 3, 6, and 12 months. METHODS: One hundred forty-five children with intractable epilepsy were randomized to receive a classical or an MCT diet. Seizure frequency was assessed after 3, 6, and 12 months. Treatment withdrawals were documented. Tolerability was assessed by questionnaire, and blood ketone levels were measured. RESULTS: Of the 61 children who started a classical diet and the 64 who started an MCT diet, data from 94 were available for analysis: 45 classical and 49 MCT. After 3, 6, and 12 months there were no statistically significant differences in mean percentage of baseline seizures between the two groups (3 months: classical 66.5%, MCT 68.9%; 6 months: classical 48.5%, MCT 67.6%; 12 months: classical 40.8%, MCT 53.2%; all p > 0.05). There were no significant differences between groups in numbers achieving greater than 50% or 90% seizure reduction. Serum acetoacetate and beta-hydroxybutyrate levels at 3 and 6 months were significantly higher in children on the classical diet (p < 0.01); this was the case at 12 months for acetoacetate. There were no significant differences in tolerability except increased reports in the classical group of lack of energy after 3 months and vomiting after 12 months. DISCUSSION: This study has shown classical and MCT ketogenic diet protocols to be comparable in efficacy and tolerability; both ways of implementing the diet have their place in the treatment of childhood epilepsy.

Timed relay contact closure controlled system for parallel second dimensions in multi-dimensional liquid chromatography.

OBJECTIVE: Short-chain triacylglycerols (TAGs) in lipid extracts of biological samples are not sufficiently resolved using conventional reversed-phase separation on two C18 columns in series, or using a two-dimensional chromatographic separation with a silver ion column as the second dimension (2D). An additional dimension of separation was required. RESULTS: The hardware and software components to allow a second second-dimension (2D) separation and three total separation dimensions were developed. Two contact closure (CC) activated 4-port, 2-position valves (4P2PVs) for ultra-high performance liquid chromatography (UHPLC) were joined together and used for one of two second dimensions in comprehensive two-dimensional liquid chromatography (2D-LC) coupled to four mass spectrometers simultaneously in parallel in an LC1MS2 × (LC1MS1 + LC1MS1) = LC3MS4 configuration. A timed contact closure circuit (TCCC) controlled the two UHPLC valves, operated by repetitive CCs for the 4P2PVs. The TCCC-controlled 4P2PVs were used to direct a portion of the 1D eluent to one of the two 2D's for separation by a quaternary UHPLC system that was not allowed by the commercial 2D-LC system. The 1D separation was a non-aqueous reversed-phase HPLC instrument used for separation of TAGs; the commercial 2D-LC 2D binary UHPLC was used for silver-ion chromatography of unsaturated TAGs; and the CC-controlled second 2D was used for separation of short-chain (SC) saturated TAGs.

A novel strategy for discriminating marine oils by using the positional distribution (sn-1, sn-2, sn-3) of omega-3 polyunsaturated fatty acids in triacylglycerols.

A novel strategy for discriminating genuine and adulterated marine oils is proposed. The strategy consists of i) determining the stereospecific distribution (sn-1, sn-2 and sn-3) of omega 3 polyunsaturated fatty acids (ω-3 PUFA) on the backbone of triacylglycerols by using liquid chromatography tandem mass spectrometry; ii) transforming the qualitative stereospecific information into quantitative data by means of a novel strategy; iii) analyzing the transformed data by principal component analysis. The proposed strategy was tested on pure oils (seal, salmon, cod liver, sandeel, blue whiting, herring), a mixture of blue whiting, herring, sandeel and Norway pout and some intentionally adulterated oils. In addition, some published krill oil data were analyzed to confirm the reliability of the new approach.

Functional diversity and nutritional content in a deep-sea faunal assemblage through total lipid, lipid class, and fatty acid analyses.

Lipids are key compounds in marine ecosystems being involved in organism growth, reproduction, and survival. Despite their biological significance and ease of measurement, the use of lipids in deep-sea studies is limited, as is our understanding of energy and nutrient flows in the deep ocean. Here, a comprehensive analysis of total lipid content, and lipid class and fatty acid composition, was used to explore functional diversity and nutritional content within a deep-sea faunal assemblage comprising 139 species from 8 phyla, including the Chordata, Arthropoda, and Cnidaria. A wide range of total lipid content and lipid class composition suggested a diversified set of energy allocation strategies across taxa. Overall, phospholipid was the dominant lipid class. While triacylglycerol was present in most taxa as the main form of energy storage, a few crustaceans, fish, jellyfishes, and corals had higher levels of wax esters/steryl esters instead. Type and amount of energy reserves may reflect dietary sources and environmental conditions for certain deep-sea taxa. Conversely, the composition of fatty acids was less diverse than that of lipid class composition, and large proportions of unsaturated fatty acids were detected, consistent with the growing literature on cold-water species. In addition, levels of unsaturation increased with depth, likely suggesting an adaptive strategy to maintain normal membrane structure and function in species found in deeper waters. Although proportions of n-3 fatty acids were high across all phyla, representatives of the Chordata and Arthropoda were the main reservoirs of these essential nutrients, thus suggesting health benefits to their consumers.

The association of the lipidomic profile with features of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) affects up to 18% of reproductive-aged women with reproductive and metabolic complications. While lipidomics can identify associations between lipid species and metabolic diseases, no research has examined the association of lipid species with the pathophysiological features of PCOS. The aim of this study was to examine the lipidomic profile in women with and without PCOS. This study was a cross-sectional study in 156 age-matched pre-menopausal women (18-45 years, BMI >20 kg/m2; n = 92 with PCOS, n = 64 without PCOS). Outcomes included the association between the plasma lipidomic profile (325 lipid species (24 classes) using liquid chromatography mass spectrometry) and PCOS, adiposity, homeostasis assessment of insulin resistance (HOMA), sex hormone-binding globulin (SHBG) and free androgen index (FAI). There were no associations of the lipidomic profile with PCOS or testosterone. HOMA was positively associated with 2 classes (dihydroceramide and triacylglycerol), SHBG was inversely associated with 2 classes (diacylglycerol and triacylglycerol), FAI was positively associated with 8 classes (ceramide, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylinositol, diacylglycerol and triacylglycerol) and waist circumference was associated with 8 classes (4 positively (dihydroceramide, phosphatidylglycerol, diacylglycerol and triacylglycerol) and 4 inversely (trihexosylceramide, GM3 ganglioside, alkenylphosphatidylcholine and alkylphosphatidylethanolamine)). The lipidomic profile was primarily related to central adiposity and FAI in women with or without PCOS. This supports prior findings that adiposity is a key driver of dyslipidaemia in PCOS and highlights the need for weight management through lifestyle interventions.

Comprehensive analysis of phospholipids and glycolipids in the opportunistic pathogen Enterococcus faecalis.

Enterococcus faecalis is a Gram-positive, opportunistic, pathogenic bacterium that causes a significant number of antibiotic-resistant infections in hospitalized patients. The development of antibiotic resistance in hospital-associated pathogens is a formidable public health threat. In E. faecalis and other Gram-positive pathogens, correlations exist between lipid composition and antibiotic resistance. Resistance to the last-resort antibiotic daptomycin is accompanied by a decrease in phosphatidylglycerol (PG) levels, whereas multiple peptide resistance factor (MprF) converts anionic PG into cationic lysyl-PG via a trans-esterification reaction, providing resistance to cationic antimicrobial peptides. Unlike previous studies that relied on thin layer chromatography and spectrophotometry, we have performed liquid chromatography-tandem mass spectrometry (LC-MS/MS) directly on lipids extracted from E. faecalis, and quantified the phospholipids through multiple reaction monitoring (MRM). In the daptomycin-sensitive E. faecalis strain OG1RF, we have identified 17 PGs, 8 lysyl-PGs (LPGs), 23 cardiolipins (CL), 3 glycerophospho-diglucosyl-diacylglycerols (GPDGDAG), 5 diglucosyl-diacylglycerols (DGDAG), 3 diacylglycerols (DAGs), and 4 triacylglycerols (TAGs). We have quantified PG and shown that PG levels vary during growth of E. faecalis in vitro. We also show that two daptomycin-resistant (DapR) strains of E. faecalis have substantially lower levels of PG and LPG levels. Since LPG levels in these strains are lower, daptomycin resistance is likely due to the reduction in PG. This lipidome map is the first comprehensive analysis of membrane phospholipids and glycolipids in the important human pathogen E. faecalis, for which antimicrobial resistance and altered lipid homeostasis have been intimately linked.

A 24-month dietary carcinogenicity study of DAG in mice.

This study evaluated the possible carcinogenic effects of DAG (diacylglycerol) oil when given in the diet at levels up to 6.0% for 24 months to mice. Dietary fat was provided by DAG and/or the control article, TG (triacylglycerol oil). Dietary concentrations (% DAG/% TG) were 0%/6.0% (TG control), 1.5%/4.5%, 3.0%/3.0%, and 6.0%/0%. An additional control group received the standard rodent diet (fat content 4.5%). The clinical condition of the animals, ophthalmic findings, palpable mass occurrence, body weights and gross and histopathologic findings were unaffected by DAG in comparison to TG. The findings in DAG-treated groups were no different than those observed in the TG control group. The standard basal diet had 4.5% fat content. Both TG and/or DAG, when presented separately or together in the diet at a total fat level of 6.0%, resulted in some differences relative to the basal diet control (lower survival, higher body weights, lower food consumption, and higher incidences of macroscopic and microscopic findings), presumably related to the higher dietary fat content and/or the semi-purified diet. However, these parameters were similar in groups fed a diet with 6.0% dietary fat that was either DAG or TG. Thus, DAG at dietary concentrations up to 6.0% for 24 months produced no signs of systemic toxicity and had no effect on the incidence of neoplastic findings.

A 24-month dietary carcinogenicity study of DAG (diacylglycerol) in rats.

Toxicologic and carcinogenic effects of DAG (diacylglycerol) oil, administered in diet for 24 months to Crl:CD((R))(SD)-IGS BR rats, were evaluated using diet-restricted and ad libitum-fed groups. All dietary fat (consistently 5.5%) was provided by DAG and/or the control article, TG (triacylglycerol) oil. Dietary concentrations (% DAG/% TG) were 0%/5.5%, 1%/4.5%, 2.75%/2.75% and 5.5%/0%. Separate groups were fed the 0%/5.5% and 5.5%/0% diets ad libitum. Another group received the standard rodent diet (fat content 4.5%) on the restricted feeding regimen. Clinical condition, ophthalmic findings, palpable mass occurrence, body composition, clinical pathology parameters and incidence of neoplastic lesions were unaffected by DAG in comparison to TG. Groups fed the 5.5% (DAG and/or TG) fat diet when compared to the 4.5% fat diet group displayed lower survival, higher body weights, organ weights, percent body fat, higher fat-related serum chemistry parameters, incidence of microscopic changes in the heart, kidneys, liver, bone marrow, spleen, and incidences of pituitary and mammary gland neoplasms. Parameters more affected in all the ad libitum groups than in the restricted diet groups (regardless of test article) fed the same diet included survival, body weights, body fat, fat-related serum chemistry parameters, and incidences of heart, kidney and liver microscopic changes. However, the DAG and TG ad libitum-fed groups were not different from one another. Thus, DAG-treated animals had no higher risk of carcinogenic effects than rats fed on similar feeding regimens with a diet in which all dietary fat came from TG.

An Unprecedented Occurrence of Δ5,9- and Δ9,15-Dienoic Fatty Acids in Ovaries of the Archaeogastropod Limpet Cellana toreuma.

A detailed structural diversity of dienoic fatty acids (FA), including non-methylene-interrupted dienoic FA, of triacylglycerols and polar lipids in ovaries of Cellana toreuma was clarified for the first time by using capillary gas chromatography-mass spectrometry of their 3-pyridylcarbinol esters and argentation thin-layer chromatography. Interestingly, in addition to 5,9-octadecadienoic (18:2Δ5,9), 5,9-eicosadienoic (20:2Δ5,9), 5,9-heneicosadienoic (21:2Δ5,9), 5,9-docosadienoic (22:2Δ5,9), 5,9-tricosadienoic (23:2Δ5,9), and 5,9-tetracosadienoic (24:2Δ5,9) acids, previously identified in ovaries of C. grata, rare FA 5,9-hexadecadienoic (16:2Δ5,9), 5,9-nonadecadienoic (19:2Δ5,9), and 21-methyl-5,9-docosadienoic (iso 23:2Δ5,9) were newly recognized in ovaries of C. toreuma. Detectable amounts of four Δ9,15-dienoic FA were present in the ovary lipids. The FA identified were one novel 9,15-heneicosadienoic (21:2Δ9,15) acid and known 9,15-docosadienoic (22:2Δ9,15), 9,15-tricosadienoic (23:2Δ9,15), and 9,15-tetracosadienoic (24:2Δ9,15) acids. The findings help to explain the broad evidence of the structural diversity in marine gastropods and suggest biomarkers to evaluate marine food web relations.

Increased T cell immunoglobulin and mucin domain containing 4 (TIM-4) is negatively correlated with serum concentrations of interleukin-1ß in type 2 diabetes.

BACKGROUND: T cell immunoglobulin and mucin domain containing 4 (TIM-4), a novel immune regulator, is selectively expressed on antigen-presenting cells, especially macrophages and mature dendritic cells. Although TIM-4 plays key roles in mutiple immune diseases, whether it is involved in type 2 diabetes mellitus (T2D) remains unknown. The aim of the present study was to investigate the expression of TIM-4 in T2D and determine its significance in disease progression. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from T2D patients and healthy controls to measure TIM-4 mRNA expression by real-time polymerase chain reaction (PCR), and sera were collected to determine interleukin (IL)-1ß concentrations and other clinical indicators (high-sensitivity C-reactive protein [hsCRP], total cholesterol, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol, triglyceride, fasting glucose, HbA1c, aspartate aminotransferase, and alanine aminotransferase). RESULTS: Expression of TIM-4 mRNA was increased significantly in PBMCs from T2D patients compared with healthy controls. There was a positive correlation between TIM-4 mRNA expression and serum concentrations of hsCRP. However, there was a negative correlation between TIM-4 mRNA expression and IL-1ß concentrations, indicating the potential role for TIM-4 to negatively regulate IL-1ß production. In addition, TIM-4 mRNA expression was negatively correlated with lowLDL-C, and there was a tendency for a negative relationship between TIM-4 mRNA expression and HbA1c. CONCLUSIONS: The results of the present study indicate that TIM-4 contributes, at least in part, to the pathogenesis of T2D, possibly by regulating IL-1ß.

Triacylglycerol molecular species are depleted to different extents in the myocardium of spontaneously hypertensive rats fed two oleic acid-rich oils.

BACKGROUND: During the development of hypertension, glucose replaces triacylglycerols (TG) as the main energy source for the myocardium. However, there are no available studies investigating the TG molecular species composition of the myocardium in the spontaneously hypertensive rat (SHR). The objective of this study was to evaluate the effect of two dietary oils (virgin olive oil [VOO] and high-oleic sunflower oil [HOSO]) with a similar oleic acid content but different TG moieties on lipid composition and especially on TG molecular species, and also the effect of on lipoprotein lipase (LPL) activity, on the SHR myocardium. METHODS: Wistar-Kyoto (WKY) rats and SHR were fed a baseline diet (BD) or a diet enriched by VOO or HOSO. Lipid classes, fatty acids of phospholipids (PL), TG, TG molecular species, and LPL were determined in the rat myocardium. RESULTS: We found a depletion of the TG pool in the myocardium of SHR, which was comcomitant with cardiac hypertrophy. The loss of this lipid class was not corrected by dietary administration and was due to a nonspecific reduction in the fatty acid content and a specific lowering of dilinoleoyl-acyl-glycerol and di-and tri-saturated TG species. In addition, we observed an increased accumulation of arachidonic acid (20:4, n-6) in the PL of the SHR group fed BD or HOSO but not in that fed VOO, as compared with the corresponding WKY. CONCLUSIONS: These results suggest that the depletion of TG in the heart of SHR is selective and is not reflected in the fatty acid profile. Although administration of either VOO or HOSO did not protect the heart against TG depletion, SHR fed VOO showed a more favorable PL compsition against changes caused by cardiac hypertrophy.

Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment.

BACKGROUND: Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects. METHOD: An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naive to abacavir and non-nucleoside reverse transcriptase inhibitors. RESULTS: At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments. CONCLUSION: In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.

Urinary organic acid excretion during feeding of medium-chain or long-chain triglyceride diets in patients with non-insulin-dependent diabetes mellitus.

Medium-chain triglycerides (MCTs) are absorbed and metabolized differently from long-chain triglycerides (LCTs). Recent data indicate that MCTs may be useful as a dietary substitute in a variety of clinical disorders. The current studies were undertaken to characterize urinary organic acid excretion in patients with non-insulin-dependent diabetes mellitus during 4 d of an LCT or MCT diet. Urinary excretion of the dicarboxylic acids adipic, suberic, and 3-hydroxysebacic and the (omega-1) hydroxylation products 5-hydroxyhexanoic acid and 7-hydroxyoctanoic acid, was increased during MCT feeding as compared with LCT feeding. Urinary suberic and 7-hydroxyoctanoic acid excretions were increased 55- and 30-fold, respectively, during the MCT-substituted diet. Urinary organic acid profiles provide information on the fate of lipids during MCT feeding and may also be useful in assessing complicance during clinical trials employing MCT-substituted diets.

Triglyceride and coronary heart disease mortality in a 24-year follow-up study in Xi'an, China.

PURPOSE: To study whether serum triglyceride (TG) was associated with coronary heart disease (CHD) mortality. METHODS: A cohort analytic study carried out in a machinery factory in Xi'an, China on 1696 subjects aged 35 years or above (1124 men and 572 women) examined in 1976 and followed up till 2000. RESULTS: At baseline, the mean serum total cholesterol (TC) and triglyceride (TG) was 4.64 and 1.16 mmol/L in men, 4.62 and 1.10 mmol/L in women, respectively. Three hundred six (239 men, 67 women) had died within 37,781 person-years of follow-up, with 49 CHD deaths (36 male, 13 female). The relative risk (95% confidence interval) of CHD mortality per mmol/L increase in TG was 2.13 (1.46-3.17) after adjusting for age, marital status, occupation, education, systolic blood pressure and TC. Dose-response relationship between TG levels by tertiles and CHD risk was found. Stratified analyses showed TG was an independent predictor for CHD mortality in subjects with lower or higher TC. CONCLUSIONS: Chinese had lower levels of TC and TG than Western populations. This study provides new evidence that TG is an independent risk factor of CHD in subjects with lower or higher TC levels, and supports the lowering of cut-off value for elevated triglyceride.