Journal of Lipids http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. ApoA-I/HDL Generation and Intracellular Cholesterol Transport through Cytosolic Lipid-Protein Particles in Astrocytes Wed, 13 Aug 2014 00:00:00 +0000 http://www.hindawi.com/journals/jl/2014/530720/ Exogenous apolipoprotein A-I (apoA-I) associates with ATP-binding cassette transporter A1 (ABCA1) on the cell surface of astrocytes like various peripheral cells and enhances the translocation of newly synthesized cholesterol from the endoplasmic reticulum/Golgi apparatus (ER/Golgi) to the cytosol. The cholesterol translocated to the cytosol is incorporated to cytosolic lipid-protein particles (CLPP) together with phospholipids and proteins such as sphingomyelin, phosphatidylcholine, caveolin-1, protein kinase Cα (PK-Cα), and cyclophilin A. The CLPP are high density lipoproteins- (HDL-)like cytosolic lipid-protein complex with densities of 1.09–1.16 g/mL and diameters of 17-18 nm. The association of exogenous apoA-I with cellular ABCA1 induces tyrosine phosphorylation, activation, and translocation to the CLPP of ABCA1-associated phospholipase Cγ (PL-Cγ) in rat astrocytes. Furthermore, PK-Cα is translocated and activated to/in the CLPP through the production of diacylglyceride in the CLPP. ApoA-I enhances both the association of CLPP with microtubules and the phosphorylation of α-tubulin as a component of microtubules. The CLPP are dissociated from microtubules after α-tubulin in microtubules is phosphorylated by the CLPP-associated PK-Cα. The association and dissociation between CLPP and microtubules may participate in the intracellular transport of cholesterol to the plasma membrane. Jinichi Ito and Makoto Michikawa Copyright © 2014 Jinichi Ito and Makoto Michikawa. All rights reserved. Physicochemical Characteristics of Citrus Seed Oils from Kerman, Iran Thu, 17 Jul 2014 09:44:41 +0000 http://www.hindawi.com/journals/jl/2014/174954/ Recently, there has been a great deal of attention on usage, byproducts, and wastes of the food industry. There have been many studies on the properties of citrus seeds and extracted oil from citrus grown in Kerman, Iran. The rate of oil content of citrus seeds varies between 33.4% and 41.9%. Linoleic acid (33.2% to 36.3%) is the key fatty acid found in citrus seeds oil and oleic (24.8% to 29.3%) and palmitic acids (23.5% to 29.4%) are the next main fatty acids, respectively. There are also other acids found at trivial rates such as stearic, palmitoleic, and linolenic. With variation between 0.54 meg/kg and 0.77 mgq/kg in peroxide values of citrus seed oils, acidity value of the oil varies between 0.44% and 0.72%. The results of the study showed that citrus seeds under study (orange and sour lemon grown in Kerman province) and the extracted oil have the potential of being used as the source of edible oil. Mohammad Reazai, Issa Mohammadpourfard, Shahrokh Nazmara, Mahdi Jahanbakhsh, and Leila Shiri Copyright © 2014 Mohammad Reazai et al. All rights reserved. Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C Thu, 17 Jul 2014 08:08:56 +0000 http://www.hindawi.com/journals/jl/2014/140723/ The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9) levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C) with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4%) were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5%) and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%). Free PCSK9 was marginally higher in nonresponders at baseline and significantly higher in atorvastatin responders after 6 months of treatment . The change in free PCSK9 over 6 months with statin treatment was higher in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy) than in either the nonresponders (39.9 ± 87.8 ng/mL) or placebo subjects (27.8 ± 97.6 ng/mL). Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment. Beth A. Taylor, Gregory Panza, Linda S. Pescatello, Stuart Chipkin, Daniel Gipe, Weiping Shao, C. Michael White, and Paul D. Thompson Copyright © 2014 Beth A. Taylor et al. All rights reserved. Comparison of Carotid Intima-Media Thickness in Pediatric Patients with Metabolic Syndrome, Heterozygous Familial Hyperlipidemia and Normals Wed, 14 May 2014 10:50:21 +0000 http://www.hindawi.com/journals/jl/2014/546863/ Background. Our goal was to compare the carotid intimal-medial thickness (CIMT) of untreated pediatric patients with metabolic syndrome (MS), heterozygous familial hyperlipidemia (heFH), and MS+heFH against one another and against a control group consisting of healthy, normal body habitus children. Methods. Our population consisted of untreated pediatric patients (ages 5–20 yrs) who had CIMT measured in a standardized manner. Results. Our population included 57 with MS, 23 with heFH, and 10 with MS+heFH. The control group consisted of 84 children of the same age range. Mean CIMT for the MS group was 469.8 μm (SD = 67), 443.8 μm (SD = 61) for the heFH group, 478.3 μm (SD = 70) for the MS+heFH group, and 423.2 μm (SD = 45) for the normal control group. Significance differences between groups occurred for heFH versus MS , heFH versus control , MS versus control , and MS+heFH versus control . Analysis showed significant negative correlation between HDL and CIMT but not for LDL, triglycerides, BP, waist circumference, or BMI. Conclusion. For pediatric patients, the thickest CIMT occurred for patients with MS alone or for those with MS+heFH. This indicates that MS, rather than just elevated LDL, accounts for more rapid thickening of CIMT in this population. Arvind Vijayasarathi and Stanley J. Goldberg Copyright © 2014 Arvind Vijayasarathi and Stanley J. Goldberg. All rights reserved. Prevalence of Dyslipidemia and Management in the Thai Population, National Health Examination Survey IV, 2009 Sun, 30 Mar 2014 12:45:20 +0000 http://www.hindawi.com/journals/jl/2014/249584/ This study determined the prevalence and management of dyslipidemia in Thai adults using data from the Thai National Health Examination Survey IV in 2009. Dyslipidemia was defined based on the Third Adult Treatment Panel guidelines. A total of 19,021 adults aged 20 yr and over were included. Mean (SE) levels of total cholesterol, HDL-C, LDL-C, and triglycerides were 206.4 (1.03), 46.9 (0.34), 128.7 (1.09), and 131.4 (2.20) mg/dL, respectively. Prevalence of high LDL-C, low HDL-C, and high triglycerides were 29.6 %, 47.1 %, and 38.6%, respectively. Compared with individuals in the north and northeast, residents in Bangkok and Central region had significant higher levels of LDL-C but lower level of HDL-C. Triglyceride level was the highest in the northeast residents. Overall, 66.5% of Thais had some forms of dyslipidemia. Awareness and treatment of high LDL-C among those with high LDL-C were 17.8% and 11.7%, respectively. Among individuals aware of high LDL-C, those at highest CHD risk compared with those at low risk had higher percentage of treatment (73.1% versus 51.7%, resp.) but lower percentage of control at goal (32.9% versus 76.4%, resp.). Various forms of dyslipidemia are common in Thai adults, with a low level of awareness and treatment of high LDL-C. Wichai Aekplakorn, Surasak Taneepanichskul, Pattapong Kessomboon, Virasakdi Chongsuvivatwong, Panwadee Putwatana, Piyamitr Sritara, Somkiat Sangwatanaroj, and Suwat Chariyalertsak Copyright © 2014 Wichai Aekplakorn et al. All rights reserved. Comparison of Low-Dose Rosuvastatin with Atorvastatin in Lipid-Lowering Efficacy and Safety in a High-Risk Pakistani Cohort: An Open-Label Randomized Trial Sun, 30 Mar 2014 08:25:20 +0000 http://www.hindawi.com/journals/jl/2014/875907/ Background. Treatment of hyperlipidemia is helpful in both primary and secondary prevention of coronary heart disease and stroke. Aim. To compare lipid-lowering efficacy of rosuvastatin with atorvastatin. Methodology. This open-label randomized controlled trial was carried out at 1 Mountain Medical Battalion from September 2012 to August 2013 on patients with type 2 diabetes, hypertension, myocardial infarction, or stroke, meriting treatment with a statin. Those with secondary causes of dyslipidemia were excluded. Blood samples for estimation of serum total cholesterol, triglycerides, HDL-C, and LDL-C were collected after a 12-hour fast. Patients were randomly allocated to receive either atorvastatin 10 mg HS or rosuvastatin 5 mg HS daily. Lipid levels were rechecked after six weeks. Results. Atorvastatin was used in 63 patients and rosuvastatin in 66. There was a greater absolute and percent reduction in serum LDL-C levels with rosuvastatin as compared to atorvastatin (0.96 versus 0.54 mg/dL; and 24.34 versus 13.66%; ), whereas reduction in all other fractions was equal. Myalgias were seen in 5 (7.94%) patients treated with atorvastatin and 8 (12.12%) patients treated with rosuvastatin (P: 0.432). Conclusion. Rosuvastatin produces a greater reduction in serum LDL-C levels and should therefore be preferred over atorvastatin. Abdul Rehman Arshad Copyright © 2014 Abdul Rehman Arshad. All rights reserved. Spice Up Your Life: Adipose Tissue and Inflammation Thu, 20 Feb 2014 12:59:55 +0000 http://www.hindawi.com/journals/jl/2014/182575/ Cells of the immune system are now recognized in the adipose tissue which, in obesity, produces proinflammatory chemokines and cytokines. Several herbs and spices have been in use since ancient times which possess anti-inflammatory properties. In this perspective, I discuss and propose the usage of these culinary delights for the benefit of human health. Anil K. Agarwal Copyright © 2014 Anil K. Agarwal. All rights reserved. Why Fish Oil Fails: A Comprehensive 21st Century Lipids-Based Physiologic Analysis Thu, 16 Jan 2014 09:16:55 +0000 http://www.hindawi.com/journals/jl/2014/495761/ The medical community suffered three significant fish oil failures/setbacks in 2013. Claims that fish oil’s EPA/DHA would stop the progression of heart disease were crushed when The Risk and Prevention Study Collaborative Group (Italy) released a conclusive negative finding regarding fish oil for those patients with high risk factors but no previous myocardial infarction. Fish oil failed in all measures of CVD prevention—both primary and secondary. Another major 2013 setback occurred when fish oil’s DHA was shown to significantly increase prostate cancer in men, in particular, high-grade prostate cancer, in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) analysis by Brasky et al. Another monumental failure occurred in 2013 whereby fish oil’s EPA/DHA failed to improve macular degeneration. In 2010, fish oil’s EPA/DHA failed to help Alzheimer’s victims, even those with low DHA levels. These are by no means isolated failures. The promise of fish oil and its so-called active ingredients EPA / DHA fails time and time again in clinical trials. This lipids-based physiologic review will explain precisely why there should have never been expectation for success. This review will focus on underpublicized lipid science with a focus on physiology. B. S. Peskin Copyright © 2014 B. S. Peskin. All rights reserved. Five Decades with Polyunsaturated Fatty Acids: Chemical Synthesis, Enzymatic Formation, Lipid Peroxidation and Its Biological Effects Mon, 30 Dec 2013 10:59:18 +0000 http://www.hindawi.com/journals/jl/2013/710290/ I have been involved in research on polyunsaturated fatty acids since 1964 and this review is intended to cover some of the most important aspects of this work. Polyunsaturated fatty acids have followed me during my whole scientific career and I have published a number of studies concerned with different aspects of them such as chemical synthesis, enzymatic formation, metabolism, transport, physical, chemical, and catalytic properties of a reconstructed desaturase system in liposomes, lipid peroxidation, and their effects. The first project I became involved in was the organic synthesis of [1-14C] eicosa-11,14-dienoic acid, with the aim of demonstrating the participation of that compound as a possible intermediary in the biosynthesis of arachidonic acid “in vivo.” From 1966 to 1982, I was involved in several projects that study the metabolism of polyunsaturated fatty acids. In the eighties, we studied fatty acid binding protein. From 1990 up to now, our laboratory has been interested in the lipid peroxidation of biological membranes from various tissues and different species as well as liposomes prepared with phospholipids rich in PUFAs. We tested the effect of many antioxidants such as alpha tocopherol, vitamin A, melatonin and its structural analogues, and conjugated linoleic acid, among others. Angel Catalá Copyright © 2013 Angel Catalá. All rights reserved. Analgesic, Anti-Inflammatory and Anticancer Activities of Extra Virgin Olive Oil Mon, 23 Dec 2013 09:10:32 +0000 http://www.hindawi.com/journals/jl/2013/129736/ Background. In folk medicine, extra virgin olive oil (EVOO) is used as a remedy for a variety of diseases. This study investigates the in vivo antinociceptive, anti-inflammatory, and anti-cancer effects of EVOO on mice and rats. Materials and Methods. In this experimental study, using the acetic acid-induced writhing and formalin tests in mice, the analgesic effect of EVOO was evaluated. Acetylsalicylic acid and morphine were used as standard drugs, respectively. The anti-inflammatory activity was investigated by means of the carrageenan-induced paw edema model in rats using acetylsalicylic acid and dexamethasone as standard drugs. Last, the xenograft model in athymic mice was used to evaluate the anticancer effect in vivo. Results. EVOO significantly decreased acetic acid-induced abdominal writhes and reduces acute and inflammatory pain in the two phases of the formalin test. It has also a better effect than Dexamethasone in the anti-inflammatory test. Finally, the intraperitoneal administration of EVOO affects the growth of HCT 116 tumours xenografted in athymic mice. Conclusion. EVOO has a significant analgesic, anti-inflammatory, and anticancer properties. However, further detailed studies are required to determine the active component responsible for these effects and mechanism pathway. Myriam Fezai, Laura Senovilla, Mohamed Jemaà, and Mossadok Ben-Attia Copyright © 2013 Myriam Fezai et al. All rights reserved. Deficiency of 25-Hydroxyvitamin D and Dyslipidemia in Indian Subjects Wed, 18 Dec 2013 15:01:47 +0000 http://www.hindawi.com/journals/jl/2013/623420/ Background. Vitamin D deficiency is widespread throughout the world. Several reports have incriminated vitamin D deficiency as the cause of rickets, osteomalacia, and other chronic diseases. Recent studies have suggested a possible link between deficiency of 25-hydroxyvitamin D and dyslipidemia. Aim. To investigate the association between 25-hydroxyvitamin D deficiency and dyslipidemia in Indian subjects. Methodology. We recruited 150 asymptomatic consecutive subjects from patients’ attendees at the Departments of Neurology and Medicine in Yashoda Hospital, Hyderabad, India. Study period was from October 2011 to March 2012. All subjects underwent 25-hydroxyvitamin D assay by chemiluminescent microparticle immunoassay, fasting blood sugar and lipid profile, calcium, phosphorus, alkaline phosphatase, and C-reactive protein (CRP). Results. Out of 150 subjects, men were 82 (54.6%), and mean age was 49.4 (±15.6) years. Among risk factors, hypertension was noted in 63/150 (42%), 25-hydroxyvitamin D deficiency in 59/150 (39.3%), diabetes in 45/150 (30%), dyslipidemia in 60 (40%), smoking in 35/150 (23.3%), and alcoholism in 27/150 (18%). Deficiency of 25-hydroxyvitamin D was significantly associated with dyslipidemia (), mean serum glucose () mean CRP (), and mean alkaline phosphatase (). Multivariate analysis showed that 25-hydroxyvitamin D deficiency was independently associated with dyslipidemia (odds ratio: 1.9; 95% CI : 1.1–3.5). Conclusions. We found that deficiency of 25-hydroxyvitamin D was independently associated with dyslipidemia in Indian subjects. Jaydip Ray Chaudhuri, K. Rukmini Mridula, Alluri Anamika, Demudu Babu Boddu, Pradeep Kumar Misra, A. Lingaiah, Banda Balaraju, and Vcs Srinivasarao Bandaru Copyright © 2013 Jaydip Ray Chaudhuri et al. All rights reserved. Antihyperlipidemic Effect of a Polyherbal Mixture in Streptozotocin-Induced Diabetic Rats Thu, 05 Dec 2013 10:54:07 +0000 http://www.hindawi.com/journals/jl/2013/675759/ The effects of a polyherbal mixture containing Allium sativum, Cinnamomum zeylanicum, Citrullus colocynthis, Juglans regia, Nigella sativa, Olea europaea, Punica granatum, Salvia officinalis, Teucrium polium, Trigonella foenum, Urtica dioica, and Vaccinium arctostaphylos were tested on biochemical parameters in diabetic rats. The animals were randomized into three groups: (1) normal control, (2) diabetic control, and (3) diabetic rats which received diet containing 15% (w/w) of this mixture for 4 weeks. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg). At the end of experiment, the mixture had no significant effect on serum hepatic enzymes, aspartate aminotransferase, and alanine aminotransferase activities. However, the level of fasting blood glucose, water intake, and urine output in treated group was lower than that in diabetic control rats (). Also, the levels of triglyceride and total cholesterol in polyherbal mixture treated rats were significantly lower than those in diabetic control group (). Our results demonstrated that this polyherbal mixture has beneficial effects on blood glucose and lipid profile and it has the potential to be used as a dietary supplement for the management of diabetes. Ahmad Ghorbani, Reza Shafiee-Nick, Hassan Rakhshandeh, and Abasalt Borji Copyright © 2013 Ahmad Ghorbani et al. All rights reserved. Grape Seed Proanthocyanidin Rescues Rats from Steatosis: A Comparative and Combination Study with Metformin Wed, 06 Nov 2013 11:50:30 +0000 http://www.hindawi.com/journals/jl/2013/153897/ Nonalcoholic fatty liver disease (NAFLD), a premorbid condition, lacks proper management owing to multitude of abnormalities. In this study, we compared the effects of a potent antioxidant, grape seed proanthocyanidins (GSP), and an insulin sensitizer, metformin (MET), in high-fat-fructose-diet- (HFFD-) induced albino Wistar rat model of NAFLD. Either GSP (100 mg/Kg b.w) or MET (50 mg/Kg b.w) or both were administered as therapeutic options. HFFD-fed rats showed abnormal plasma lipid profile, inflammation, and steatosis of the liver when examined by biochemical and histology techniques. Increased lipid storage, lipogenesis, and reduced lipolysis were evident from mRNA expression studies of hepatic lipid droplets (LD) proteins, sterol regulatory element binding 1c (SREBP 1c), and peroxisome proliferator activated receptor-α (PPAR-α). GSP administration to HFFD-fed rats caused 69% reduction in hepatic TG levels, whereas MET caused only 23%. The combination treatment reduced TG levels by 63%. GSP reduced the mRNA expression of SREBP1c and LD proteins and increased that of PPAR-α more effectively compared to MET in HFFD-induced hyperlipidemic rats. Combination of MET and GSP improved the metabolism of lipids effectively, but the effect was not additive in restoring lipid levels. Baskaran Yogalakshmi, S Sreeja, Rajagopalan Geetha, Mutlur Krishnamoorthy Radika, and Carani Venkatraman Anuradha Copyright © 2013 Baskaran Yogalakshmi et al. All rights reserved. Association of RXR-Gamma Gene Variants with Familial Combined Hyperlipidemia: Genotype and Haplotype Analysis Sun, 13 Oct 2013 15:15:07 +0000 http://www.hindawi.com/journals/jl/2013/517943/ Background. Familial combined hyperlipidemia (FCHL), the most common genetic form of hyperlipdemia, is characterized by a strong familial clustering and by premature coronary heart disease. The FCHL locus has been mapped to human chromosome 1q21-q23. This region includes the retinoid X receptor gamma (RXRG), a nuclear factor member of the RXR superfamily, which plays important roles in lipid homeostasis. Objective. To investigate the possible role of the RXRG gene in the genetic susceptibility to FCHL. Methods. Variations in RXRG gene were searched by direct sequencing, and the identified SNPs were genotyped by PCR-RFLP in 192 FCHL individuals from 74 families and in 119 controls. Results. We identified 5 polymorphisms in the RXRG gene (rs1128977, rs2651860, rs2134095, rs283696, and rs10918169). Genotyping showed that the A-allele of rs283696 SNP was significantly associated with FCHL (corrected , ). Also the alleles of the rs10918169 and of the rs2651860 SNP were more frequent in FCHL subjects compared to those in controls, although not significantly after correction. When the clinical characteristics of the FCHL subjects were stratified by allele carrier status for each SNP, the rs2651860 SNP was significantly associated with increased levels of LDL-cholesterol and of Apo-B in T-allele carriers . Finally, haplotypes analysis with all 5 SNPs confirmed the significant association of RXRG gene with FCHL. Specifically, the haplotype containing all 3 “at-risk” alleles, significantly associated with FCHL (A-allele of rs283696, G-allele of rs10918169, and T-allele of rs2651860), showed an OR (Odds Ratio) of 2.02, . Conversely, the haplotype without all these 3 alleles was associated with a reduced risk for FCHL (, ). The “at-risk” haplotype CTTAG was also associated with higher LDL-C . In conclusion, variation in the RXRG gene may contribute to the genetic dyslipidemia in FCHL subjects. Federica Sentinelli, Ilenia Minicocci, Anna Montali, Luisa Nanni, Stefano Romeo, Michela Incani, M. Gisella Cavallo, Andrea Lenzi, Marcello Arca, and Marco G. Baroni Copyright © 2013 Federica Sentinelli et al. All rights reserved. Reduction of Cellular Lipid Content by a Knockdown of Drosophila PDP1γ and Mammalian Hepatic Leukemia Factor Thu, 22 Aug 2013 08:37:31 +0000 http://www.hindawi.com/journals/jl/2013/297932/ In exploring the utility of double-stranded RNA (dsRNA) injections for silencing the PAR-domain protein 1 (Pdp1) gene in adult Drosophila, we noticed a dramatic loss of fat tissue lipids. To verify that our RNAi approach produced the expected Pdp1 knockdown, the abdominal fat tissues sections were stained with PDP1 antibodies. PDP1 protein immunostaining was absent in flies injected with dsRNA targeting a sequence common to all known Pdp1 isoforms. Subsequent experiments revealed that lipid staining is reduced in flies injected with dsRNA against Pdp1γ (fat body specific) and not against Pdp1ε (predominantly involved in circadian mechanisms). Drosophila PDP1γ protein shows a high homology to mammalian thyrotroph embryonic factor (TEF), albumin D site-binding protein (DBP), and hepatic leukemia factor (HLF) transcription factors. In an in vitro model of drug- (olanzapine-) induced adiposity in mouse 3T3-L1 cells, the mRNA content of HLF but not TEF and DBP was increased by the drug treatment. A knockdown of the HLF mRNA by transfecting the cultures with HLF dsRNA significantly reduced their lipid content. Furthermore, the HLF RNAi prevented olanzapine from increasing the cell lipid content. These results suggest that the PDP1/HLF system may play a role in physiological and drug-influenced lipid regulation. Svetlana Dzitoyeva and Hari Manev Copyright © 2013 Svetlana Dzitoyeva and Hari Manev. All rights reserved. Sphingolipid Metabolic Pathway: An Overview of Major Roles Played in Human Diseases Sun, 04 Aug 2013 14:19:24 +0000 http://www.hindawi.com/journals/jl/2013/178910/ Sphingolipids, a family of membrane lipids, are bioactive molecules that participate in diverse functions controlling fundamental cellular processes such as cell division, differentiation, and cell death. Given that most of these cellular processes form the basis for several pathologies, it is not surprising that sphingolipids are key players in several pathological processes. This review discusses the role of the sphingolipid metabolic pathway in diabetes, Alzheimer’s disease, and hepatocellular carcinoma, with a special emphasis on the changes in gene expression pattern in these disease conditions. For convenience, the sphingolipid metabolic pathway is divided into hypothetical compartments (modules) with each compartment representing a physiological process and changes in gene expression pattern are mapped to each of these modules. It appears that alterations in the gene expression pattern in these disease conditions are biased to manipulate the system in order to result in a particular disease. Raghavendra Pralhada Rao, Nanditha Vaidyanathan, Mathiyazhagan Rengasamy, Anup Mammen Oommen, Neeti Somaiya, and M. R. Jagannath Copyright © 2013 Raghavendra Pralhada Rao et al. All rights reserved. Treadmill Exercise Training Modulates Hepatic Cholesterol Metabolism and Circulating PCSK9 Concentration in High-Fat-Fed Mice Wed, 19 Jun 2013 08:55:14 +0000 http://www.hindawi.com/journals/jl/2013/908048/ Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel biomarker of LDL clearance and a therapeutic target of cardiovascular disease. We examined the effects of aerobic exercise training in modulating PCSK9 abundance and hepatic sterol regulation in high-fat-fed C57BL/6 mice. Mice () were assigned to a low-fat (LF), high-fat (HF), or an HF with exercise (HF + EX) group for 8 weeks. The HF + EX group was progressively trained 5 days/week on a motorized treadmill. The HF + EX group was protected against body weight (BW) gain and diet-induced dyslipidemia compared with the HF group. The HF + EX group demonstrated an increase in hepatic PCSK9 mRNA (1.9-fold of HF control, ) and a reduction in plasma PCSK9 (14%) compared with the HF group. Compared with HF mice, HF + EX mice demonstrated reduced hepatic cholesterol (14%) and increased () nuclear SREBP2 protein (1.8-fold of HF group) and LDLr mRNA (1.4-fold of HF group). Plasma PCSK9 concentrations correlated positively with plasma non-HDL-C (, ). Results suggest that treadmill exercise reduces non-HDL cholesterol and differentially modulates hepatic and blood PCSK9 abundance in HF-fed C57BL/6 mice. Shin Wen, Kavita S. Jadhav, David L. Williamson, and Todd C. Rideout Copyright © 2013 Shin Wen et al. All rights reserved. 5-Lipoxygenase-Activating Protein as a Modulator of Olanzapine-Induced Lipid Accumulation in Adipocyte Sat, 25 May 2013 15:55:30 +0000 http://www.hindawi.com/journals/jl/2013/864593/ Experiments were performed in 3T3-L1 preadipocytes differentiated in vitro into adipocytes. Cells were treated with olanzapine and a 5-lipoxygenase (5-LOX) activating protein (FLAP) inhibitor MK-886. Lipid content was measured using an Oil Red O assay; 5-LOX and FLAP mRNA content was measured using quantitative real-time PCR; the corresponding protein contents were measured using quantitative Western blot assay. Olanzapine did not affect the cell content of 5-LOX mRNA and protein; it decreased FLAP mRNA and protein content at day five but not 24 hours after olanzapine addition. In the absence of MK-886, low concentrations of olanzapine increased lipid content only slightly, whereas a 56% increase was induced by 50 μM olanzapine. A 5-day cotreatment with 10 μM MK-886 potentiated the lipid increasing action of low concentrations of olanzapine. In contrast, in the presence of 50 μM olanzapine nanomolar and low micromolar concentrations of MK-886 reduced lipid content. These data suggest that FLAP system in adipocytes is affected by olanzapine and that it may modify how these cells respond to the second-generation antipsychotic drugs (SGADs). Clinical studies could evaluate whether the FLAP/5-LOX system could play a role in setting a variable individual susceptibility to the metabolic side effects of SGADs. Svetlana Dzitoyeva, Hu Chen, and Hari Manev Copyright © 2013 Svetlana Dzitoyeva et al. All rights reserved. The Multifaceted Effects of Omega-3 Polyunsaturated Fatty Acids on the Hallmarks of Cancer Thu, 16 May 2013 14:12:46 +0000 http://www.hindawi.com/journals/jl/2013/261247/ Omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid, and docosahexaenoic acid have been shown to have multiple beneficial antitumour actions that affect the essential alterations that dictate malignant growth. In this review we explore the putative mechanisms of action of omega-3 polyunsaturated fatty acid in cancer protection in relation to self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion, and how these will hopefully translate from bench to bedside. J. A. Stephenson, O. Al-Taan, A. Arshad, B. Morgan, M. S. Metcalfe, and A. R. Dennison Copyright © 2013 J. A. Stephenson et al. All rights reserved. Trans-10, cis 12-Conjugated Linoleic Acid-Induced Milk Fat Depression Is Associated with Inhibition of PPAR Signaling and Inflammation in Murine Mammary Tissue Tue, 14 May 2013 14:48:04 +0000 http://www.hindawi.com/journals/jl/2013/890343/ Exogenous trans-10, cis-12-CLA (CLA) reduces lipid synthesis in murine adipose and mammary (MG) tissues. However, genomewide alterations in MG and liver (LIV) associated with dietary CLA during lactation remain unknown. We fed mice (/diet) control or control + trans-10, cis-12-CLA (37 mg/day) between d 6 and d 10 postpartum. The 35,302 annotated murine exonic evidence-based oligo (MEEBO) microarray and quantitative RT-PCR were used for transcript profiling. Milk fat concentration was 44% lower on d 10 versus d 6 due to CLA. The CLA diet resulted in differential expression of 1,496 genes. Bioinformatics analyses underscored that a major effect of CLA on MG encompassed alterations in cellular signaling pathways and phospholipid species biosynthesis. Dietary CLA induced genes related to ER stress (Xbp1), apoptosis (Bcl2), and inflammation (Orm1, Saa2, and Cp). It also induced marked inhibition of PPARγ signaling, including downregulation of Pparg and Srebf1 and several lipogenic target genes (Scd, Fasn, and Gpam). In LIV, CLA induced hepatic steatosis probably through perturbations in the mitochondrial functions and induction of ER stress. Overall, results from this study underscored the role of PPARγ signaling on mammary lipogenic target regulation. The proinflammatory effect due to CLA could be related to inhibition of PPARγ signaling. Anil K. G. Kadegowda, M. Jawad Khan, Liliana S. Piperova, Beverly B. Teter, Sandra L. Rodriguez-Zas, Richard A. Erdman, and Juan J. Loor Copyright © 2013 Anil K. G. Kadegowda et al. All rights reserved. Roles of Fatty Acid Oversupply and Impaired Oxidation in Lipid Accumulation in Tissues of Obese Rats Mon, 13 May 2013 14:13:45 +0000 http://www.hindawi.com/journals/jl/2013/420754/ To test the roles of lipid oversupply versus oxidation in causing tissue lipid accumulation associated with insulin resistance/obesity, we studied in vivo fatty acid (FA) metabolism in obese (Obese) and lean (Lean) Zucker rats. Indices of local FA utilization and storage were calculated using the partially metabolizable [9,10-3H]-(R)-2-bromopalmitate (3H-R-BrP) and [U-14C]-palmitate (14C-P) FA tracers, respectively. Whole-body FA appearance () was estimated from plasma 14C-P kinetics. Whole-body FA oxidation rate () was assessed using 3H2O production from 3H-palmitate infusion, and tissue FA oxidative capacity was evaluated ex vivo. In the basal fasting state Obese had markedly elevated FA levels and , associated with elevated FA utilization and storage in most tissues. Estimated rates of muscle FA oxidation were not lower in obese rats and were similarly enhanced by contraction in both lean and obese groups. At comparable levels of FA availability, achieved by nicotinic acid, was lower in Obese than Lean. In Obese rats, FA oxidative capacity was 35% higher than that in Lean in skeletal muscle, 67% lower in brown fat and comparable in other organs. In conclusion, lipid accumulation in non-adipose tissues of obese Zucker rats appears to result largely from systemic FA oversupply. Nicholas D. Oakes, Ann Kjellstedt, Pia Thalén, Bengt Ljung, and Nigel Turner Copyright © 2013 Nicholas D. Oakes et al. All rights reserved. Modification of Phospholipid Bilayers Induced by Sulfurated Naphthoquinones Sat, 30 Mar 2013 14:14:56 +0000 http://www.hindawi.com/journals/jl/2013/592318/ New thionaphthoquinones and their hydroxyl derivatives, bearing alkyl side chains that match the phospholipids POPC and POPE, were synthesized in order to investigate their interactions with lipids. It was observed that, in general, these additives destabilize the lipid bilayer and induce less organized structures with higher curvature, in particular the induction of an hexagonal phase on aqueous POPC mixtures. Moreover, cubic phases, not normally observed in the pure lipids when fully hydrated, were detected. Coexistence of lamellar phases was interpreted as a consequence of microsegregation of the components in the mixtures. These results are in line with previous observations on the effect of structurally similar (hydro)quinones in phase behavior of these lipids. Claudio Di Vitta, Liliana Marzorati, and Sérgio S. Funari Copyright © 2013 Claudio Di Vitta et al. All rights reserved. PPARγ Networks in Cell Signaling: Update and Impact of Cyclic Phosphatidic Acid Thu, 07 Feb 2013 11:27:49 +0000 http://www.hindawi.com/journals/jl/2013/246597/ Lysophospholipid (LPL) has long been recognized as a membrane phospholipid metabolite. Recently, however, the LPL has emerged as a candidate for diagnostic and pharmacological interest. LPLs include lysophosphatidic acid (LPA), alkyl glycerol phosphate (AGP), cyclic phosphatidic acid (cPA), and sphingosine-1-phosphate (S1P). These biologically active lipid mediators serve to promote a variety of responses that include cell proliferation, migration, and survival. These LPL-related responses are mediated by cell surface G-protein-coupled receptors and also intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). In this paper, we focus mainly on the most recent findings regarding the biological function of nuclear receptor-mediated lysophospholipid signaling in mammalian systems, specifically as they relate to health and diseases. Also, we will briefly review the biology of PPARγ and then provide an update of lysophospholipids PPARγ ligands that are under investigation as a therapeutic compound and which are targets of PPARγ relevant to diseases. Tamotsu Tsukahara Copyright © 2013 Tamotsu Tsukahara. All rights reserved. The Impairment of Macrophage-to-Feces Reverse Cholesterol Transport during Inflammation Does Not Depend on Serum Amyloid A Wed, 30 Jan 2013 13:35:00 +0000 http://www.hindawi.com/journals/jl/2013/283486/ Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with 3H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. 3H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of 3H-cholesterol was unaltered in either WT or SAAKO mice by LPS treatment. Radioactivity present in bile and feces of LPS-injected WT mice 24 hr after macrophage injection was reduced by 36%   and 80%  , respectively. In contrast, in SAAKO mice, LPS did not significantly reduce macrophage-derived 3H-cholesterol in bile, and fecal excretion was reduced by only 45%  . Injection of cholesterol-loaded allogeneic J774 cells, but not syngeneic bone-marrow-derived macrophages, transiently induced SAA in C57BL/6 mice. Our study confirms reports that acute inflammation impairs steps in the RCT pathway and establishes that SAA plays only a minor role in this impairment. Maria C. de Beer, Joanne M. Wroblewski, Victoria P. Noffsinger, Ailing Ji, Jason M. Meyer, Deneys R. van der Westhuyzen, Frederick C. de Beer, and Nancy R. Webb Copyright © 2013 Maria C. de Beer et al. All rights reserved. High-Density Lipoproteins and the Immune System Wed, 30 Jan 2013 13:18:17 +0000 http://www.hindawi.com/journals/jl/2013/684903/ High-density lipoprotein (HDL) plays a major role in vasodilation and in the reduction of low-density lipoprotein (LDL) oxidation, inflammation, apoptosis, thrombosis, and infection; however, HDL is now less functional in these roles under certain conditions. This paper focuses on HDL, its anti-inflammation behavior, and the mechanisms by which HDL interacts with components of the innate and adaptive immune systems. Genome-wide association studies (GWAS) and proteomic studies have elucidated important molecules involved in the interaction between HDL and the immune system. An understanding of these mechanisms is expected to be useful for the prevention and treatment of chronic inflammation due to metabolic syndrome, atherosclerosis, or various autoimmune diseases. Hidesuke Kaji Copyright © 2013 Hidesuke Kaji. All rights reserved. Molecular Characterization of Lipopolysaccharide Binding to Human α-1-Acid Glycoprotein Thu, 20 Dec 2012 09:22:15 +0000 http://www.hindawi.com/journals/jl/2012/475153/ The ability of AGP to bind circulating lipopolysaccharide (LPS) in plasma is believed to help reduce the proinflammatory effect of bacterial lipid A molecules. Here, for the first time we have characterized human AGP binding characteristics of the LPS from a number of pathogenic Gram-negative bacteria: Escherichia coli, Salmonella typhimurium, Klebsiella pneumonia, Pseudomonas aeruginosa, and Serratia marcescens. The binding affinity and structure activity relationships (SAR) of the AGP-LPS interactions were characterized by surface plasma resonance (SPR). In order to dissect the contribution of the lipid A, core oligosaccharide and O-antigen polysaccharide components of LPS, the AGP binding affinity of LPS from smooth strains, were compared to lipid A, Kdo2-lipid A, , , and rough LPS mutants. The SAR analysis enabled by the binding data suggested that, in addition to the important role played by the lipid A and core components of LPS, it is predominately the unique species- and strain-specific carbohydrate structure of the O-antigen polysaccharide that largely determines the binding affinity for AGP. Together, these data are consistent with the role of AGP in the binding and transport of LPS in plasma during acute-phase inflammatory responses to invading Gram-negative bacteria. Johnny X. Huang, Mohammad A. K. Azad, Elizabeth Yuriev, Mark A. Baker, Roger L. Nation, Jian Li, Matthew A. Cooper, and Tony Velkov Copyright © 2012 Johnny X. Huang et al. All rights reserved. Sphingosine 1-Phosphate Distribution in Human Plasma: Associations with Lipid Profiles Thu, 08 Nov 2012 15:17:48 +0000 http://www.hindawi.com/journals/jl/2012/180705/ The physiological significance of sphingosine 1-phosphate (S1P) transport in blood has been debated. We have recently reported a comprehensive sphingolipid profile in human plasma and lipoprotein particles (VLDL, LDL, and HDL) using HPLC-MS/MS (Hammad et al., 2010). We now determined the relative concentrations of sphingolipids including S1P in the plasma subfraction containing lipoproteins compared to those in the remaining plasma proteins. Sphingomyelin and ceramide were predominantly recovered in the lipoprotein-containing fraction. Total plasma S1P concentration was positively correlated with S1P concentration in the protein-containing fraction, but not with S1P concentration in the lipoprotein-containing fraction. The percentage of S1P transported in plasma lipoproteins was positively correlated with HDL cholesterol (HDL-C) concentration; however, S1P transport in lipoproteins was not limited by the concentration of HDL-C in the individual subject. Thus, different plasma pools of S1P may have different contributions to S1P signaling in health and disease. Samar M. Hammad, Mohammed M. Al Gadban, Andrea J. Semler, and Richard L. Klein Copyright © 2012 Samar M. Hammad et al. All rights reserved. Hepatic Metabolic, Inflammatory, and Stress-Related Gene Expression in Growing Mice Consuming a Low Dose of Trans-10, cis-12-Conjugated Linoleic Acid Sun, 02 Sep 2012 14:26:08 +0000 http://www.hindawi.com/journals/jl/2012/571281/ Dietary trans-10, cis-12-conjugated linoleic acid (trans-10, cis-12-CLA) fed to obese and nonobese rodents reduces body fat but leads to greater liver mass due to steatosis. The molecular mechanisms accompanying such responses remain largely unknown. Our study investigated the effects of chronic low trans-10, cis-12-CLA supplementation on hepatic expression of 39 genes related to metabolism, inflammation, and stress in growing mice. Feeding a diet supplemented with 0.3% trans-10, cis-12-CLA (wt/wt basis) for 6 weeks increased liver mass and concentration of long-chain fatty acids (LCFAs) in liver, while adipose tissue mass decreased markedly. These changes were accompanied by greater expression of genes involved in LCFA uptake (Cd36), lipogenesis, and triacylglycerol synthesis (Acaca, Gpam, Scd, Pck1, Plin2). Expression of these genes was in line with upregulation of the lipogenic transcription factor Srebf1. Unlike previous studies where higher >0.50% of the diet) doses of trans-10, cis-12-CLA were fed, we found greater expression of genes associated with VLDL assembly/secretion (Mttp, Cideb), ketogenesis (Hmgcs2, Bdh1), and LCFA oxidation (Acox1, Pdk4) in response to trans-10, cis-12-CLA. Dietary CLA, however, did not affect inflammation- and stress-related genes. Results suggested that a chronic low dose of dietary CLA increases liver mass and lipid accumulation due to activation of lipogenesis and insufficient induction of LCFA oxidation and VLDL assembly/secretion. Jing Li, Srikant Viswanadha, and Juan J. Loor Copyright © 2012 Jing Li et al. All rights reserved. Dietary Omega-3 Fatty Acids Do Not Change Resistance of Rat Brain or Liver Mitochondria to Ca2+ and/or Prooxidants Mon, 27 Aug 2012 13:22:36 +0000 http://www.hindawi.com/journals/jl/2012/797105/ Omega-3 polyunsaturated fatty acids (n-3 PUFAs) block apoptotic neuronal cell death and are strongly neuroprotective in acute and chronic neurodegeneration. Theoretical considerations, indirect data, and consideration of parsimony lead to the hypothesis that modulation of mitochondrial pathway(s) underlies at least some of the neuroprotective effects of n-3 PUFAs. We therefore systematically tested this hypothesis on healthy male FBFN1 rats fed for four weeks with isocaloric, 10% fat-containing diets supplemented with 1, 3, or 10% fish oil (FO). High resolution mass spectrometric analysis confirmed expected diet-driven increases in docosahexaenoic acid (DHA, 22:6, n-3) and eicosapentaenoic acid (EPA, 20:5, n-3) in sera, liver and nonsynaptosomal brain mitochondria. We further evaluated the resistance of brain and liver mitochondria to Ca2+ overload and prooxidants. Under these conditions, neither mitochondrial resistance to Ca2+ overload and prooxidants nor mitochondrial physiology is altered by diet, despite the expected incorporation of DHA and EPA in mitochondrial membranes and plasma. Collectively, the data eliminate one of the previously proposed mechanism(s) that n-3 PUFA induced augmentation of mitochondrial resistance to the oxidant/calcium-driven dysfunction. These data furthermore allow us to define a specific series of follow-up experiments to test related hypotheses about the effect of n-3 PUFAs on brain mitochondria. Irina G. Stavrovskaya, Susan S. Bird, Vasant R. Marur, Sergei V. Baranov, Heather K. Greenberg, Caryn L. Porter, and Bruce S. Kristal Copyright © 2012 Irina G. Stavrovskaya et al. All rights reserved. Fatty Acid Composition of Phospholipids and in the Central and External Positions of Triacylglycerol in Muscle and Subcutaneous Fat of Beef Steers Fed Diets Supplemented with Oil Containing n6 and n3 Fatty Acids While Undergoing One of Three 48 h Feed Withdrawal Treatments Sun, 29 Jul 2012 09:51:24 +0000 http://www.hindawi.com/journals/jl/2012/543784/ This study was designed to determine the effects of dietary oil and feed withdrawal treatments on fatty acid composition of phospholipids of triacylglycerol in pars costalis diaphragmatis muscle and subcutaneous fat from the brisket. A 2 × 3 factorial experiment was conducted with crossbred steers with an initial body weight of 280.5 ± 5.8 kg. Steers were fed either a control or an oil containing diet where 5% of the control diet was replaced with an equal mixture sunflower and flax oil while undergoing one of three feed withdrawal treatments: no withdrawal, a single 48 h withdrawal before initiation of fattening at one year of age, or 48 h withdrawal at 8 wk intervals from weaning to initiation of fattening. At time of processing samples of muscle and fat were obtained and analyzed to determine fatty acid composition. Disproportionate distribution of the fatty acids was observed by diet, feed withdrawal regimen and whether the sample was from muscle or fat. Differences are discussed in detail, and our data suggests a special function for the fatty acids that accumulate in specific positions of the triacylglycerol due to treatment. C. Margetak, G. Travis, T. Entz, P. S. Mir, S. Wei, and M. V. Dodson Copyright © 2012 C. Margetak et al. All rights reserved.