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Lipid Accumulation (lipid + accumulation)
Selected AbstractsInsulin resistance and fuel homeostasis: the role of AMP-activated protein kinaseACTA PHYSIOLOGICA, Issue 1 2009B. D. Hegarty Abstract The worldwide prevalence of type 2 diabetes (T2D) and related disorders of the metabolic syndrome (MS) has reached epidemic proportions. Insulin resistance (IR) is a major perturbation that characterizes these disorders. Extra-adipose accumulation of lipid, particularly within the liver and skeletal muscle, is closely linked with the development of IR. The AMP-activated protein kinase (AMPK) pathway plays an important role in the regulation of both lipid and glucose metabolism. Through its effects to increase fatty acid oxidation and inhibit lipogenesis, AMPK activity in the liver and skeletal muscle could be expected to ameliorate lipid accumulation and associated IR in these tissues. In addition, AMPK promotes glucose uptake into skeletal muscle and suppresses glucose output from the liver via insulin-independent mechanisms. These characteristics make AMPK a highly attractive target for the development of strategies to curb the prevalence and costs of T2D. Recent insights into the regulation of AMPK and mechanisms by which it modulates fuel metabolism in liver and skeletal muscle are discussed here. In addition, we consider the arguments for and against the hypothesis that dysfunctional AMPK contributes to IR. Finally we review studies which assess AMPK as an appropriate target for the prevention and treatment of T2D and MS. [source] The role of intramuscular lipid in insulin resistanceACTA PHYSIOLOGICA, Issue 4 2003B. D. Hegarty Abstract There is interest in how altered lipid metabolism could contribute to muscle insulin resistance. Many animal and human states of insulin resistance have increased muscle triglyceride content, and there are now plausible mechanistic links between muscle lipid accumulation and insulin resistance, which go beyond the classic glucose,fatty acid cycle. We postulate that muscle cytosolic accumulation of the metabolically active long-chain fatty acyl CoAs (LCACoA) is involved, leading to insulin resistance and impaired insulin signalling or impaired enzyme activity (e.g. glycogen synthase or hexokinase) either directly or via chronic translocation/activation of mediators such as a protein kinase C (particularly PKC , and ,). Ceramides and diacylglycerols (DAGs) have also been implicated in forms of lipid-induced muscle insulin resistance. Dietary lipid-induced muscle insulin resistance in rodents is relatively easily reversed by manipulations that lessen cytosolic lipid accumulation (e.g. diet change, exercise or fasting). PPAR agonists (both , and ,) also lower muscle LCACoA and enhance insulin sensitivity. Activation of AMP-activated protein kinase (AMPK) by AICAR leads to muscle enhancement (especially glycolytic muscle) of insulin sensitivity, but involvement of altered lipid metabolism is less clear cut. In rodents there are similarities in the pattern of muscle lipid accumulation/PKC translocation/altered insulin signalling/insulin resistance inducible by 3,5-h acute free fatty acid elevation, 1,4 days intravenous glucose infusion or several weeks of high-fat feeding. Recent studies extend findings and show relevance to humans. Muscle cytosolic lipids may accumulate either by increased fatty acid flux into muscle, or by reduced fatty acid oxidation. In some circumstances muscle insulin resistance may be an adaptation to optimize use of fatty acids when they are the predominant available energy fuel. The interactions described here are fundamental to optimizing therapy of insulin resistance based on alterations in muscle lipid metabolism. [source] Effects of cevoglitazar, a dual PPAR,/, agonist, on ectopic fat deposition in fatty Zucker ratsDIABETES OBESITY & METABOLISM, Issue 6 2009D. Laurent Aim:, By acting as both insulin sensitizers and lipid-lowering agents, dual-acting peroxisome proliferator-activated receptors ,/, (PPAR,/,) agonists may be used to improve glucose tolerance in type 2 diabetic patients without inducing adiposity and body weight gain. Here, in an animal model of obesity and insulin resistance, the metabolic response to cevoglitazar, a dual PPAR,/,, was characterized using a combination of in vivo and ex vivo magnetic resonance methodologies and compared to treatment effects of fenofibrate, a PPAR, agonist, and pioglitazone, a PPAR, agonist. Methods:, Four groups of fatty Zucker rats: (i) Vehicle; (ii) fenofibrate 150 mg/kg; (iii) pioglitazone 30 mg/kg; and (iv) cevoglitazar 5 mg/kg were investigated before and after treatment. Animals were fed a fat-enriched (54% kcal fat) diet for 6 weeks, 2 weeks high of fat,exposure alone followed by a 4-week dosing period. Results and conclusions:, Cevoglitazar was as effective as pioglitazone at improving glucose tolerance. However, unlike pioglitazone, both fenofibrate and cevoglitazar reduced BW gain and adiposity, independent of food intake. All three treatment regimens normalized intramyocellular lipids. Metabolic profiling showed that in the muscle cevoglitazar improves the lipid profile via both PPAR,- and PPAR,-mediated mechanisms. Pioglitazone reduced hepatic lipid accumulation, while cevoglitazar and fenofibrate reduced hepatic lipid concentration below baseline levels (p < 0.05). Metabolic profiling showed that in the liver, cevoglitazar functions largely through PPAR, agonism resulting in increased ,-oxidation. Cevoglitazar only induced small changes to the lipid composition of visceral fat. In subcutaneous fat, however, cevoglitazar induced changes similar to those observed with fenofibrate suggesting export of fatty acids from this depot. [source] Metformin inhibits intracellular lipid accumulation in the murine pre-adipocyte cell line, 3T3-L1DIABETES OBESITY & METABOLISM, Issue 8 2008K. B. Alexandre No abstract is available for this article. [source] 8-isoprostane increases scavenger receptor A and matrix metalloproteinase activity in THP-1 macrophages, resulting in long-lived foam cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2004H. Scholz Abstract Background, Oxidative stress is a key factor in atherogenesis, in which it is closely associated with the inflammation and formation of bioactive lipids. Although 8-isoprostane is regarded as a reliable marker of oxidative stress in vivo, the pathogenic role of this F2 -isoprostane in atherogenesis is far from clear. Based on the important role of foam cells in the initiation and progression of atherosclerosis we hereby examined the ability of 8-isoprostane to modulate oxidized (ox)LDL-induced foam cell formation and the function of these cells, particularly focusing on the effect on matrix degradation. Methods and results, 8-isoprostane (10 µM) augmented the oxLDL-induced (20 µg mL,1) lipid accumulation of THP-1 macrophages evaluated by Oil-Red-O staining and lipid mass quantification (colourimetric assay). Additionally, 8-isoprostane induced the expression of the scavenger receptor A type 1 (MSR-1) [mRNA and protein level], assessed by RT-PCR and Western blotting, respectively. Moreover, 8-isoprostane counteracted the oxLDL-induced apoptosis of these cells, involving both mitochondrial-protective and caspase-suppressive mechanisms. Along with these changes, 8-isoprostane increased the oxLDL-induced gene expression of matrix metalloproteinase (MMP)-9 and its endogenous inhibitor [i.e. tissue inhibitor of MMP (TIMP)-1] accompanied by enhanced total MMP activity. Conclusions, We show that 8-isoprostane increases foam cell formation at least partly by enhancing MSR-1 expression and by inhibiting apoptosis of these cells, inducing long-lived foam cells with enhanced matrix degrading capacity. Our findings further support a role for 8-isoprostane not only as a marker of oxidative stress in patients with atherosclerotic disorders, but also as a mediator in atherogenesis and plaque destabilization. [source] Differential alteration of lipid antigen presentation to NKT cells due to imbalances in lipid metabolismEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2007Jens Schümann Abstract Deficiencies in enzymes of the lysosomal glycosphingolipid degradation pathway or in lysosomal lipid transfer proteins cause an imbalance in lipid metabolism and induce accumulation of certain lipids. A possible impact of such an imbalance on the presentation of lipid antigens to lipid-reactive T cells has only been hypothesized but not extensively studied so far. Here we demonstrate that presentation of lipid antigens to, and development of, lipid-reactive CD1d-restricted NKT cells, are impaired in mice deficient in the lysosomal enzyme ,-galactosidase (,Gal) or the lysosomal lipid transfer protein Niemann-Pick C (NPC) 2. Importantly, the residual populations of NKT cells selected in ,Gal,/, and NPC2,/, mice showed differential TCR and CD4 repertoire characteristics, suggesting that differential selecting CD1d:lipid antigen complexes are formed. Furthermore, we provide direct evidence that accumulation of lipids impairs lipid antigen presentation in both cases. However, the mechanisms by which imbalanced lipid metabolism affected lipid antigen presentation were different. Based on these results, the impact of lipid accumulation should be generally considered in the interpretation of immunological deficiencies found in mice suffering from lipid metabolic disorders. [source] Glycation of low-density lipoprotein results in the time-dependent accumulation of cholesteryl esters and apolipoprotein B-100 protein in primary human monocyte-derived macrophagesFEBS JOURNAL, Issue 6 2007Bronwyn E. Brown Nonenzymatic covalent binding (glycation) of reactive aldehydes (from glucose or metabolic processes) to low-density lipoproteins has been previously shown to result in lipid accumulation in a murine macrophage cell line. The formation of such lipid-laden cells is a hallmark of atherosclerosis. In this study, we characterize lipid accumulation in primary human monocyte-derived macrophages, which are cells of immediate relevance to human atherosclerosis, on exposure to low-density lipoprotein glycated using methylglyoxal or glycolaldehyde. The time course of cellular uptake of low-density lipoprotein-derived lipids and protein has been characterized, together with the subsequent turnover of the modified apolipoprotein B-100 (apoB) protein. Cholesterol and cholesteryl ester accumulation occurs within 24 h of exposure to glycated low-density lipoprotein, and increases in a time-dependent manner. Higher cellular cholesteryl ester levels were detected with glycolaldehyde-modified low-density lipoprotein than with methylglyoxal-modified low-density lipoprotein. Uptake was significantly decreased by fucoidin (an inhibitor of scavenger receptor SR-A) and a mAb to CD36. Human monocyte-derived macrophages endocytosed and degraded significantly more 125I-labeled apoB from glycolaldehyde-modified than from methylglyoxal-modified, or control, low-density lipoprotein. Differences in the endocytic and degradation rates resulted in net intracellular accumulation of modified apoB from glycolaldehyde-modified low-density lipoprotein. Accumulation of lipid therefore parallels increased endocytosis and, to a lesser extent, degradation of apoB in human macrophages exposed to glycolaldehyde-modified low-density lipoprotein. This accumulation of cholesteryl esters and modified protein from glycated low-density lipoprotein may contribute to cellular dysfunction and the increased atherosclerosis observed in people with diabetes, and other pathologies linked to exposure to reactive carbonyls. [source] Heterologous expression of AtClo1, a plant oil body protein, induces lipid accumulation in yeastFEMS YEAST RESEARCH, Issue 3 2009Marine Froissard Abstract Proteomic approaches on lipid bodies have led to the identification of proteins associated with this compartment, showing that, rather than the inert fat depot, lipid droplets appear as complex dynamic organelles with roles in metabolism control and cell signaling. We focused our investigations on caleosin [Arabidopsis thaliana caleosin 1 (AtClo1)], a minor protein of the Arabidopsis thaliana seed lipid body. AtClo1 shares an original triblock structure, which confers to the protein the capacity to insert at the lipid body surface. In addition, AtClo1 possesses a calcium-binding domain. The study of plants deficient in caleosin revealed its involvement in storage lipid degradation during seed germination. Using Saccharomyces cerevisiae as a heterologous expression system, we investigated the potential role of AtClo1 in lipid body biogenesis and filling. The green fluorescent protein-tagged protein was correctly targeted to lipid bodies. We observed an increase in the number and size of lipid bodies. Moreover, transformed yeasts accumulated more fatty acids (+46.6%). We confirmed that this excess of fatty acids was due to overaccumulation of lipid body neutral lipids, triacylglycerols and steryl esters. We showed that the original intrinsic properties of AtClo1 protein were sufficient to generate a functional lipid body membrane and to promote overaccumulation of storage lipids in yeast oil bodies. [source] Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes,HEPATOLOGY, Issue 5 2007Cheng Ji Betaine-homocysteine methyltransferase (BHMT) regulates homocysteine levels in the liver. We previously reported that the alteration of BHMT is associated with alcoholic liver steatosis and injury. In this study, we tested whether BHMT protects hepatocytes from homocysteine-induced injury and lipid accumulation. Both BHMT transfectants of HepG2 cells and primary mouse hepatocytes with suppressed BHMT were generated. Comparisons were made between the cell models with respect to their response to homocysteine treatments. Homocysteine metabolism was impaired in HepG2 cells, and the expression of BHMT in HepG2 cells ameliorated the impairment and stabilized the levels of intracellular homocysteine after the addition of exogenous homocysteine. BHMT expression inhibited homocysteine-induced glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) and homocysteine-induced cell death. A betaine treatment protected primary mouse hepatocytes from a homocysteine-induced increase in GRP78 and cell death but not a tunicamycin-induced increase. Homocysteine induced greater CHOP expression (2.7-fold) in BHMT small interfering RNA (siRNA),transfected cells than in a control (1.9-fold). Homocysteine-induced cell death was increased by 40% in the siRNA-treated cells in comparison with the control. Apolipoprotein B (apoB) expression was higher and triglycerides and cholesterol were lower in HepG2 expressing BHMT. In primary mouse hepatocytes, homocysteine induced the accumulation of triglycerides and cholesterol, which was reduced in the presence of betaine. Betaine partially reduced homocysteine-induced sterol regulatory element binding protein 1 expression in HepG2 cells and increased S-adenosylmethionine in primary mouse hepatocytes. Conclusion: The BHMT/betaine system directly protects hepatocytes from homocysteine-induced injury but not tunicamycin-induced injury, including an endoplasmic reticulum stress response, lipid accumulation, and cell death. This system also exhibits a more generalized effect on liver lipids by inducing ApoB expression and increasing S-adenosylmethionine/S-adenosylhomocysteine. (HEPATOLOGY 2007.) [source] Induction of hepatotoxicity by sanguinarine is associated with oxidation of protein thiols and disturbance of mitochondrial respirationJOURNAL OF APPLIED TOXICOLOGY, Issue 8 2008Cheuk-Sing Choy Abstract Sanguinarine (SANG) has been suggested to be one of the principle constituents responsible for the toxicity of Argemone mexicana seed oil. In this study, we focused on the possible mechanism of SANG-induced hepatotoxicity. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, hepatic vacuolization, lipid accumulation and lipid peroxidation of the liver were increased, and triglyceride (TG) was decreased in SANG-treated mice (10 mg kg,1 i.p.), indicating damage to the liver. SANG induced cell death and DNA fragmentation, in a concentration- (0,30 µm) and time-dependent (0,24 h) manner, and the cytotoxicity of SANG (15 µm) was accompanied by an increase in reactive oxygen species and a lessening in protein thiol content; these outcomes were reversed by glutathione, N -acetyl- l -cysteine and 1,4-dithiothretol, and slightly improved by other antioxidants in hepatocytes. SANG can affect the function of mitochondria, leading to the depletion of the mitochondrial membrane potential and adenosine 5,-triphosphate content of hepatocytes. SANG caused an uncoupling effect of the respiratory chain at lower concentrations, but inhibited the respiratory chain at higher concentrations in mitochondria isolated from rat liver. In conclusion, the data suggest that SANG is a liver toxin that induces cytotoxicity in liver cells, possibly through oxidation of protein thiols, resulting in oxidative stress on the cells and disturbance of mitochondrial function. Copyright © 2008 John Wiley & Sons, Ltd. [source] Comparative energy allocation in two sympatric, closely related gobies: the black goby Gobius niger and the grass goby Zosterisessor ophiocephalusJOURNAL OF FISH BIOLOGY, Issue 2 2007R. Fiorin Seasonal energy allocation of lipid reserves into different body tissues was analysed comparatively in two sympatric, closely related gobies: the grass goby Zosterisessor ophiocephalus and the black goby Gobius niger. Lipid reserves were measured in liver, muscle and ovary and compared between the two species within a given sex and seasonal period (reproductive v. non-reproductive). Furthermore, temporal patterns of lipid reserves were investigated in the two species in relation to gonado-somatic and liver-somatic indices, as well as the relationship between size and lipid content. Results showed that the grass goby allocated more lipid reserves in reproduction while the black goby accumulated more reserves in liver and muscle, at a given size, although the temporal patterns of lipid accumulation and depletion were basically similar. Results are discussed in the light of life-history theories, taking into account both adaptation and evolutionary constraints. [source] Energy allocation in juvenile sablefish: effects of temperature, ration and body sizeJOURNAL OF FISH BIOLOGY, Issue 3 2004S. M. Sogard The lipid deposition of juvenile sablefish Anoplopoma fimbria was examined, in particular, the changes in allocation over time. Growth rates of early juveniles (initial size 36,50 mm total length, LT) were manipulated using two temperatures (10 and 20° C) and two rations (ad libitum and 3,4% body mass day,1). Fish LT, mass and lipid content were measured every 3 weeks for 15 weeks. Irrespective of treatment, the relationship of total lipid content with body size was clearly hyperallometric; small juveniles allocated relatively more energy to growth and less to lipid storage than large juveniles. After adjusting for the influence of body size, temperature and ration significantly influenced body composition but these effects varied over the course of the experiment. In the first 3 week time period, fish on the high ration, high temperature treatment had reduced lipid storage relative to other treatments, but in all subsequent time periods their lipid concentrations were similar to or higher than those of fish on other treatments. In contrast, fish held at low rations and low temperatures initially had average levels of lipid concentration, but after 6 weeks their levels were lower than other treatments. Estimation of allocation to lipid storage over time (proportion of dry mass increase comprised of lipid) suggested that fish in all of the treatments were approaching an asymptotic level of lipid concentration (c. 50,60% of dry mass) but with different rates of lipid increase. Within a treatment, it was predicted that individual differences in allocation would result in trade-offs between somatic growth and storage. This trade-off was evident only for fish held on low rations at low temperatures. In contrast, fish held on high rations at high temperatures exhibited the opposite pattern of a positive correlation between somatic growth and storage. These results suggest that lipostatic regulation of appetite is unlikely in juvenile sablefish. When resources are unlimited, this species appears to adopt a maximizing strategy for both somatic growth and lipid accumulation. [source] Ultrastructural pathology of Baltic salmon, Salmo salar L., yolk sac fry with the M74 syndromeJOURNAL OF FISH DISEASES, Issue 3 2002J Lundström The ultrastructural pathology in liver, brain, skeletal and cardiac muscle of Baltic salmon yolk sac fry with the M74 syndrome is described. In the clinical stage of disease, the main pathological findings in the liver were a depletion of glycogen, condensation of nuclear chromatin, hydropic degeneration of mitochondria and a dilation of the bile canaliculi. In the terminal stage, additional findings were lipid accumulation and myelin whorls in the cytoplasm. The rough endoplasmic reticulum (RER) was degranulated and vesiculated and in some individuals, it formed concentric membranous whorls. Mitochondria showed several additional lesions, such as matrix densities, pleomorphism and cristae abnormalities. Skeletal myocytes were degenerated, and intracellular lipid accumulation was seen in the myocardium. In the brain, an increased frequency of cells exhibiting pyknosis or karryorhexis was recorded. The cytoplasm of these cells formed an amorphous mass of moderate density. The evaluation of brain and skeletal muscle was complicated by sporadic occurrence of pathological findings in the reference material, i.e. clinically healthy Baltic salmon yolk sac fry. As these yolk sac fry are suspected to have a subclinical thiamine deficiency, reference material in future studies should include salmon yolk sac fry from Atlantic populations or originating from reared broodstock. [source] Mechanobiological response of tendon stem cells: Implications of tendon homeostasis and pathogenesis of tendinopathyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2010Jianying Zhang Abstract Tendons are constantly subjected to mechanical loading in vivo. Recently, stem cells were identified in human, mouse, and rabbit tendons, but the mechanobiological responses of tendon stem cells (TSCs) are still undefined. Using an in vitro system capable of mimicking in vivo loading conditions, it was determined that mechanical stretching increased TSC proliferation in a stretching magnitude-dependent manner. Moreover, low mechanical stretching at 4% ("clamp-to-clamp" engineering strain) promoted differentiation of TSCs into tenocytes, whereas large stretching at 8% induced differentiation of some TSCs into adipogenic, chondrogenic, and osteogenic lineages, as indicated by upregulated expression of marker genes for adipocytes, chondrocytes, and osteocytes. Thus, low mechanical stretching may be beneficial to tendons by enabling differentiation of TSCs into tenocytes to maintain tendon homeostasis. However, large mechanical loading may be detrimental, as it directs differentiation of TSCs into non-tenocytes in tendons, thus resulting in lipid accumulation, mucoid formation, and tissue calcification, which are typical features of tendinopathy at later stages. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:639,643, 2010 [source] Periodontitis-induced lipid peroxidation in rat descending aorta is involved in the initiation of atherosclerosisJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2009D. Ekuni Background and Objective:, Periodontitis is a risk factor for the development of atherosclerosis. Recent studies indicate that oxidative mechanisms, including lipid peroxidation, are involved not only in periodontitis but also in atherosclerosis. Lipid peroxidation may play an important role in the pathogenesis of atherosclerosis, particularly during its earliest stages. The purpose of this study was to investigate the relationship between lipid peroxidation induced by periodontitis and the initiation of atherosclerosis. Material and Methods:, Sixteen rats were randomly divided into two groups of eight rats each. Periodontitis was ligature-induced for 4 wk in the experimental group, whereas the control group was left untreated. After the experimental period, the mandibular first molar regions were resected and then subjected to histological analysis and measurement of hexanoyl-lysine expression as an indicator of lipid peroxidation. Descending aorta was used for measuring the levels of hexanoyl-lysine, reactive oxygen species and lipid deposits, and for real-time polymerase chain reaction microarray analysis. The level of hexanoyl-lysine was also measured in serum. Results:, In the experimental group, the levels of hexanoyl-lysine in periodontal tissue and serum increased. Only aorta samples in the experimental group showed lipid accumulation, with increased expression of hexanoyl-lysine, reactive oxygen species and oxidative stress-related genes (including nitric oxide synthases 2 and 3), whereas the superoxide dismutase 1 gene level was down-regulated. Conclusion:, In a ligature-induced periodontitis rat model, increased lipid peroxidation was found in serum and aorta as well as in periodontal tissue. Atherosclerosis-related gene expression and histological changes were also stimulated. Periodontitis-induced lipid peroxidation in the aorta may be involved in the early stage of atherosclerosis. [source] PLASTID FATTY ACID BIOSYNTHESIS IN THE DIATOMS NITZSCHIA ALBA AND NITZSCHIA LAEVISJOURNAL OF PHYCOLOGY, Issue 2000K.M. McGinnis The role of the plastid in fatty acid biosynthesis in the non-photosynthetic diatom Nitzschia alba was studied and compared to that in the photosynthetic, closely related Nitzschia laevis. Transmission electron microscopy was used to analyze structural features of the plastid that may be relevant to biochemical function. Typical of a photosynthetic diatom, N. laevis had a chloroplast envelope composed of four membranes, and had abundant chloroplast ribosomes. The leucoplast of N. alba also had a multi-membrane envelope, chloroplast ribosomes, and a genome that encodes plastid specific proteins. This suggested that the plastid of N. alba may still possess the biochemical functions of the chloroplast, aside from photosynthesis. To determine whether plastidial fatty acid biosynthesis occurred in N. alba, the response of the two diatoms to the compound thiolactomycin was compared. Thiolactomycin has been shown to effect keto-acyl-ACP-synthases, and specifically inhibits the plastidial fatty acid biosynthetic pathway. While growth of N. alba was not impacted by thiolactomycin as in N. laevis, neutral lipid accumulation and fatty acid composition was impacted by thiolactomycin in both organisms. These findings suggest that the plastidial fatty acid biosynthetic pathway does exist in the leucoplast of N. alba, although it lacks photosynthetic capacity. [source] Delayed changes in T1 -weighted signal intensity in a rat model of 15-minute transient focal ischemia studied by magnetic resonance imaging/spectroscopy and synchrotron radiation X-ray fluorescenceMAGNETIC RESONANCE IN MEDICINE, Issue 3 2006Xuxia Wang Abstract Previous studies have found that rats subjected to 15-min transient middle cerebral artery occlusion (MCAO) show neurodegeneration in the dorsolateral striatum only, and the resulting striatal lesion is associated with increased T1 -weighted (T1W) signal intensity (SI) and decreased T2 -weighted (T2W) SI at 2,8 weeks after the initial ischemia. It has been shown that the delayed increase in T1W SI in the ischemic region is associated with deposition of paramagnetic manganese ions. However, it has been suggested that other mechanisms, such as tissue calcification and lipid accumulation, also contribute to the relaxation time changes. To clarify this issue, we measured changes in relaxation times, lipid accumulation, and elemental distributions in the brain of rats subjected to 15-min MCAO using MRI, in vivo 1H MR spectroscopy (MRS), and synchrotron radiation X-ray fluorescence (SRXRF). The results show that a delayed (2 weeks after ischemia) increase in T1W SI in the ischemic striatum is associated with significant increases in manganese, calcium, and iron, but without evident accumulation of MRS-visible lipids or hydroxyapatite precipitation. It was also found that 15-min MCAO results in acutely reduced N-acetylaspartate (NAA)/creatine (Cr) ratio in the ipsilateral striatum, which recovers to the control level at 2 weeks after ischemia. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] Protein hydrolysates from ,-conglycinin enriched soybean genotypes inhibit lipid accumulation and inflammation in vitroMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 8 2009Cristina Martinez-Villaluenga Abstract Obesity is a worldwide health concern and a well recognized predictor of premature mortality associated with a state of chronic inflammation. The objective was to evaluate the effect of soy protein hydrolysates (SPH) produced from different soybean genotypes by alcalase (SAH) or simulated gastrointestinal digestion (SGIH) on lipid accumulation in 3T3-L1 adipocytes. The anti-inflammatory effect of SPH produced by alcalase on LPS-induced macrophage RAW 264.7 cell line was also investigated. SAH (100 ,M) derived from soybean enriched in ,-conglycinin (BC) (up to 47% total protein) decreased lipid accumulation (33,37% inhibition) through downregulation of gene expression of lipoprotein lipase (LPL) and fatty acid synthase (FAS). SGIH (100 ,M) inhibited lipid accumulation to a lesser extent (8,14% inhibition) through inhibition of LPL gene expression. SAH (5 ,M) decreased the production of nitric oxide (NO) (18,35%) and prostaglandin E2 (PGE2) (47,71%) and the expression of inducible nitric oxide synthase (iNOS) (31,53%) and cycloxygenase-2 (COX-2) (30,52%). This is the first investigation showing that soy hydrolysates inhibit LPS-induced iNOS/NO and COX-2/PGE2 pathways in macrophages. Soybeans enriched in BCs can provide hydrolysates that limit fat accumulation in fat cells and inflammatory pathways in vitro and therefore warrant further studies as a healthful food. [source] Dietary Calcium and Dairy Modulation of Adiposity and Obesity RiskNUTRITION REVIEWS, Issue 4 2004Michael B. Zemel Ph.D. Dietary calcium plays a key role in the regulation of energy metabolism and obesity risk. This appears to be mediated primarily by dietary calcium modulation of circulating calcitriol, which in turn regulates adipocyte intracellular calcium ([Ca2+]i). Increased [Ca2]i stimulates lipogenic gene expression and activity and inhibits lipolysis, resulting in increased adipocyte lipid accumulation. Since calcitriol stimulates adipocyte Ca2+ influx, low calcium diets promote adiposity, while dietary calcium-suppression of calcitriol reduces adiposity. These concepts are confirmed in controlled rodent studies as well as by epidemiological and clincial trial data, all of which confirm protection from obesity with high calcium intakes. Moreover, dairy sources of calcium exert markedly greater effects which are most likely attributable to additional bioactive compounds in dairy which act synergistically with calcium to attenuate adiposity. [source] Resveratrol induces apoptosis and inhibits adipogenesis in 3T3-L1 adipocytes ,PHYTOTHERAPY RESEARCH, Issue 10 2008Srujana Rayalam Abstract Resveratrol, a phytoallexin, has recently been reported to slow aging by acting as a sirtuin activator. Resveratrol also has a wide range of pharmacological effects on adipocytes. In this study, we investigated the effects of resveratrol on adipogenesis and apoptosis using 3T3-L1 cells. In mature adipocytes, 100 and 200 µM resveratrol decreased cell viability dose-dependently by 23 ± 2.7%, and 75.3 ± 2.8% (p < 0.0001), respectively, after 48 h treatment, and 100 µM resveratrol increased apoptosis by 76 ± 8.7% (p < 0.0001). Resveratrol at 25 and 50 µM decreased lipid accumulation in maturing preadipocytes significantly by 43 ± 1.27% and 94.3 ± 0.3% (p < 0.0001) and decreased cell viability by 25 ± 1.3% and 70.4 ± 1.6% (p < 0.0001), respectively. In order to understand the anti-adipogenic effects of resveratrol, maturing 3T3-L1 preadipocytes were treated with 25 µM resveratrol and the change in the expression of several adipogenic transcription factors and enzymes was investigated using real-time RT-PCR. Resveratrol down-regulated the expression of PPAR,, C/EBP,, SREBP-1c, FAS, HSL, LPL and up-regulated the expression of genes regulating mitochondrial activity (SIRT3, UCP1 and Mfn2). These results indicate that resveratrol may alter fat mass by directly affecting cell viability and adipogenesis in maturing preadipocytes and inducing apoptosis in adipocytes and thus may have applications for the treatment of obesity. Copyright © 2008 John Wiley & Sons, Ltd. [source] Aqueous extract of rhubarb stabilizes vulnerable atherosclerotic plaques due to depression of inflammation and lipid accumulationPHYTOTHERAPY RESEARCH, Issue 7 2008Yunfang Liu Abstract The study evaluated the effect of the traditional Chinese medicine rhubarb on the stability of atherosclerotic plaque. Atherosclerotic lesions were induced in rabbits through balloon injury with a high-cholesterol diet and then were divided into a control group, a rhubarb group and a simvastatin group. At week 24 recombinant-p53 adenoviruses were locally delivered to the atherosclerotic plaques. At week 26 plaque rupture was triggered by the intra-arterial Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathologic, immunohistochemical and gene expression studies were performed. The results showed that the incidence of plaque rupture in the rhubarb group and the simvastatin group was significantly lower than that in the control group (42.86% and 35.71% versus 80.00%, both p < 0.05). Serum TC, LDL-C (p < 0.05,0.01), IMT (both p < 0.01), PA (both p < 0.01), PB (%) (both p < 0.01) and the mRNA and protein expressions of TLR2, TLR4 and NF- ,B (p < 0.05, 0.01, respectively) in the rhubarb group and the simvastatin group were significantly lower than those in the control group. In contrast, AIIc% (both p < 0.05) in the two treatment groups were significantly higher than those in the control group. These results suggest that rhubarb has antiatherosclerotic and plaque-stabilizing properties due to antiinflammation and lipid-lowering effects. Copyright © 2008 John Wiley & Sons, Ltd. [source] Pharmacological effects of fermented red pepperPHYTOTHERAPY RESEARCH, Issue 11 2004Y. M. Choi Abstract The pharmacological effects were investigated of fermented red pepper (HF-S), which consisted of 14.7% carbohydrate, 1.5% lipid, 4.9% protein, 0.3% ash, 78.2% moisture content, with 0.15% capsaicin and 0.06% dihydrocapsaicin. Oral administration of 0.25 mL HF-S for 3 weeks produced signi,cant changes of the perirenal fat pad weight compared with the HF-control group, suggesting a suppressive effect on lipid accumulation and a signi,cant decrease in the risk of arteriosclerosis. The HF-S (0.25 mL) group also showed a lower plasma TG, TC level and atherogenic index than that of the HF-control. In addition, the HF-S (0.25 mL) group showed a marked increase in the production of glutathione, which is the major endogenous antioxidant, and a decrease in the production of lipid peroxide as the product of chemical damage by oxygen free radicals. It is assumed that the effect of HF-S might relate to high glutathione production on the suppression of lipid peroxidation. HF-S stimulated not only the proliferation of macrophages (as high as the positive control, LPS at 1000 µg/mL) but also mitogenic activity (1.2-fold of LPS at 100 µg/mL). Copyright © 2004 John Wiley & Sons, Ltd. [source] Plant-extract-induced changes in the proteome of the soil-borne pathogenic fungus Thielaviopsis basicolaPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 8 2010Joëlle V. F. Coumans Abstract Thielaviopsis basicola is a hemibiotroph fungus that causes black root rot disease in diverse plants with significant impact on cotton production in Australia. To elucidate how T. basicola growth and proteome are influenced by interactions with natural sources, this fungus was cultured in the presence of root extracts from non-host (wheat, hairy vetch) and susceptible host (cotton, lupin) plants. We found that T. basicola growth was significantly favored in the presence of host extracts, while hierarchical clustering analysis of 2-DE protein profiles of T. basicola showed plant species had a larger effect on the proteome than host/non-host status. Analysis by LC-MS/MS of unique and differentially expressed spots and identification using cross-species similarity searching and de novo sequencing allowed successful identification of 41 spots. These proteins were principally involved in primary metabolism with smaller numbers implicated in other diverse functions. Identification of several "morpho" proteins suggested morphological differences that were further microscopically investigated. Identification of several highly expressed spots suggested that vitamin B6 is important in the T. basicola response to components present in hairy vetch extract, and finally, three spots, induced in the presence of lupin extract, may correspond to malic enzyme and be involved in lipid accumulation. [source] An optimum method designed for 2-D DIGE analysis of human arterial intima and media layers isolated by laser microdissectionPROTEOMICS - CLINICAL APPLICATIONS, Issue 10 2009Fernando de la Cuesta Abstract The formation and progression of atherosclerotic lesions involve complex mechanisms which are still not fully understood. A variety of cell types from the distinct arterial layers are implicated in the whole process from lipid accumulation within the vascular wall to plaque development and final rupture. In the present work, we employ the combination of laser microdissection and pressure catapulting and 2-D DIGE saturation labeling to investigate the human intima and media sub-proteomes isolated from atherosclerotic (coronary and aorta) or non-atherosclerotic vessels (preatherosclerotic coronary arteries). Laser microdissection and pressure catapulting allows the specific isolation of regions of interest. In turn, DIGE saturation labeling overcomes the limitation of extensive microdissection times to recover the protein amount required to perform comparative 2-DE, particularly when dealing with tissue regions rich in myofilament proteins, which result in low protein recovery. The compatibility and optimum performance of both techniques were investigated in detail, paying special attention to tissue staining and protein solubilization. Since scarce amount of protein obtained from microdissected tissue made it impossible to directly perform protein identification from 2-DE spots by MS, we performed in-solution digestion followed by LC-MS/MS analysis of total protein extracts from intima and media in order to get an overall picture of protein composition. Proteins so identified confirm the nature of the isolated regions. Finally, similar spot resolution on 2-D DIGE gels was obtained for the different human artery types (coronary, aorta) and studied layers (intima, media), setting the basis for future clinical comparative studies. [source] Myocardial metabolism of triacylglycerol-rich lipoproteins in type 2 diabetesTHE JOURNAL OF PHYSIOLOGY, Issue 13 2009You-Guo Niu Cardiac utilisation of very-low-density lipoprotein (VLDL) and chylomicrons (CM) was investigated in the ZDF rat model of type 2 diabetes, in order to define the role of triacylglycerol (TAG) metabolism in the development of contractile dysfunction. Hearts from obese diabetic and lean littermate control rats were perfused with VLDL and CM from diabetic and control rats. Metabolic fate of the lipoprotein TAG and contractile function were examined. Myocardial utilisation of both VLDL- and CM-TAG was increased in the diabetic state. Diabetic hearts oxidised diabetic lipoprotein-TAG to a greater extent than control lipoproteins; glucose oxidation was decreased. There was no difference in lipoprotein-TAG assimilation into diabetic heart lipids; diabetic lipoproteins were, however, a poor substrate for control heart tissue lipid accumulation. Although the proportion of exogenous lipid incorporated into tissue TAG was increased in diabetic hearts perfused with control lipoproteins, this effect was not seen in diabetic hearts perfused with diabetic lipoproteins. Myocardial heparin-releasable lipoprotein lipase (LPL) activity was moderately increased in the diabetic state, and diabetic lipoproteins increased tissue-residual LPL activity. Cardiac hydraulic work was decreased only in diabetic hearts perfused with diabetic CM. Compositional analysis of diabetic variant lipoproteins indicated changes in size and apoprotein content. Alterations in cardiac TAG-rich lipoprotein metabolism in type 2 diabetes are due to changes in both the diabetic myocardium and the diabetic lipoprotein particle; decreased contractile function is not related to cardiac lipid accumulation from TAG-rich lipoproteins but may be associated with changes in TAG-fatty acid oxidation. [source] Dicer ablation in oligodendrocytes provokes neuronal impairment in mice,ANNALS OF NEUROLOGY, Issue 6 2009Daesung Shin PhD Objective MicroRNAs (miRNAs) regulate gene expression and have many roles in the brain, but a role in oligodendrocyte (OL) function has not been demonstrated. Methods A Dicer floxed conditional allele was crossed with the proteolipid protein promoter-driven inducible Cre allele to generate inducible, OL-specific Dicer -floxed mice. Results OL-specific Dicer mutants show demyelination, oxidative damage, inflammatory astrocytosis and microgliosis in the brain, and eventually neuronal degeneration and shorter lifespan. miR-219 and its target ELOVL7 (elongation of very long chain fatty acids protein 7) were identified as the main molecular components that are involved in the development of the phenotype in these mice. Overexpressing ELOVL7 results in lipid accumulation, which is suppressed by miR-219 co-overexpression. In Dicer mutant brain, excess lipids accumulate in myelin-rich brain regions, and the peroxisomal ,-oxidation activity is dramatically reduced. Interpretation Postnatal Dicer ablation in mature OLs results in inflammatory neuronal degeneration through increased demyelination, lipid accumulation, and peroxisomal and oxidative damage, and therefore indicates that miRNAs play an essential role in the maintenance of lipids and redox homeostasis in mature OLs that are necessary for supporting axonal integrity as well as the formation of compact myelin. Ann Neurol 2009;66:843,857 [source] Comparison of starch utilization in fingerlings of two Asian catfishes from the Mekong River (Pangasius bocourti Sauvage, 1880, Pangasius hypophthalmus Sauvage, 1878)AQUACULTURE NUTRITION, Issue 4 2003L. T. Hung Abstract Five diets were formulated to provide an isoproteic daily dietary intake of 15 g kg,1 day,1, while maintaining daily starch intake ranging from 0 to 40 g kg,1 day,1. The 4-week experiments started with initial mean weights of 4.7 and 4.4 g for Pangasius bocourti and P. hypophthalmus, respectively. The results clearly show the protein sparing action of starch in both species. Best protein retention was obtained with starch intake of 20 and 10 g kg,1 day,1 for P. bocourti and P. hypophthalmus, respectively, which was equivalent to 40 and 20% starch in the feed. Pangasius bocourti and P. hypophthalmus fingerlings attained maximal growth with starch intake of 30 and 10 g kg,1 day,1, equivalent to 60 and 20% starch in the feed. It was noted that body lipid accumulation was much higher in P. bocourti than in P. hypophthalmus, and that excess dietary starch intake depressed diet digestibility and growth. [source] Long-term Administration of Rapamycin Reduces Adiposity, but Impairs Glucose Tolerance in High-Fat Diet-fed KK/HlJ MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2009Geng-Ruei Chang In this study, we investigated the metabolic effects of rapamycin in an obese animal model, KK/HlJ mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle for 42 days on a high-fat diet. Treated mice lost body weight and adiposity, reduced weight gain and retroperitoneal and epididymal fat pads/body weight, decreased serum leptin and plasma triglyceride levels and had lower liver fat concentration. However, treated mice had higher serum insulin levels and food intake. Dissection of rapamycin-treated mice revealed a marked reduction in fatty liver scores and fat cell size in retroperitoneal and epididymal adipocytes. Moreover, Western blot analysis revealed that rapamycin treatment resulted in decreasing adipophilin expression, as a marker of lipid accumulation, and reducing phosphorylation of mTOR downstream targets S6K1 compared to control group. Unfortunately, rapamycin-treated animals showed a marked decline in glucose tolerance as judged by the 180-min. area under the curve for plasma glucose levels, paralleled by increased generation of plasma reactive oxygen species. These results suggest that continual rapamycin administration may help to prevent diet-induced obesity, while prolonged use of rapamycin may exacerbate glucose intolerance. [source] Enhanced pro-apoptotic and anti-adipogenic effects of genistein plus guggulsterone in 3T3-L1 adipocytesBIOFACTORS, Issue 3 2007Jeong-Yeh Yang Abstract Genistein (G), an isoflavone, and guggulsterone (GS), the active substance in guggulipid, have been reported to possess therapeutic effects for obesity. In the present study, we investigated the effects of combinations of G plus GS on apoptosis and adipogenesis in 3T3-L1 cells. In mature adipocytes, G and GS individually caused apoptosis, but combination of G plus GS significantly increased apoptosis, more than either compound alone. Furthermore, G plus GS caused a greater increase in procaspase-3 cleavage, Bax expression, cytochrome c release, and proteolytic cleavage of PARP than either compound alone. In maturing preadipocytes G and GS each suppressed lipid accumulation, but the combination potentiated the inhibition of lipid accumulation. These results suggest that combination of genistein and guggulsterone may exert anti-obesity effects by inhibiting adipogenesis and inducing apoptosis in adipocytes. [source] Anti-adipogenic effects of Garcinia extract on the lipid droplet accumulation and the expression of transcription factorBIOFACTORS, Issue 1-4 2004Myung-Sunny Kim Abstract Garcinia extract was used as a potential anti-obesity agent. In this study, we found that Garcinia extract inhibits the cytoplasmic lipid accumulation as well as adipogenic differentiation of preadipocytes. The mechanisms that regulate the inhibition of insulin-induced differentiation by Garcinia extracts include the inhibition of expression of the early adipogenic transcription factor, CCAAT element binding protein (C/EBP), that regulate adipogenesis. These results suggest that the specific targets of Garcinia extract on differentiation process of 3T3-L1 cells could be, at least, early adipogenic differentiation factor. [source] | |||||||||||||||||||