Triglyceride deficiency and diacylglycerol kinase1 activity lead to the upregulation of mevalonate pathway in yeast: A study for the development of potential yeast platform for improved production of triterpenoid.

Besides energy storage and membrane biogenesis, lipids are known for their numerous biological functions. The two essential lipids, diacylglycerol (DG) and phosphatidic acid (PA), are shown to be associated with cell signalling processes. In this study, we examined whether triglyceride-deficient yeast mutants (tgΔ), dga1Δ and dga1Δlro1Δ, may play an important role in mevalonate (MEV) pathway regulation. Our metabolite analyses revealed that tgΔ cells showed high levels of squalene (SQ) and ergosterol (ERG), which are key indicators of MEV pathway activity. In addition, gene expression studies indicated that the MEV pathway genes in tgΔ cells were significantly upregulated. Interestingly, tgΔ cells exhibited high diacylglycerol kinase1 (DGK1) expression. Furthermore, DGK1 overexpression in WT and tgΔ phenotypes causes a substantial elevation in SQ and ERG levels, and we also found a significant increase in transcript levels of MEV pathway genes, confirming the new role of DGK1 in MEV pathway regulation. This suggests that high DG phosphorylation activity increases the PA pool that may induce the upregulation of MEV pathway in tgΔ cells. The induced MEV pathway is one of the key strategies in the field of synthetic biology for improved production of terpenoids in yeast. Thus, to examine whether increased endogenous MEV pathway flux can be redirected to triterpenoid, ß-Amyrin synthase gene was heterologously expressed in DGK1 overexpressing tgΔ cells that led to significant production of ß-Amyrin, a natural triterpenoid. In conclusion, our findings provide a novel strategy to increase MEV pathway precursors by modulating endogenous signal lipids for improved production of terpenoids.

Overproduction of altered VLDL in an insulin-resistance rat model: influence of SREBP-1c and PPAR-X / Sobreproducción de VLDL alteradas en un modelo de insulinorresistencia de rata: influencia de SREBP-1c y PPAR-x

Background: In insulin-resistance, VLDL presents alterations that increase its atherogenic potential. The mechanism by which insulin-resistance promotes the production of altered VLDL is still not completely understood. The aim of this study was to evaluate the relationship between the expression of sterol regulatory element binding protein 1c (SREBP-1c) and of peroxisome proliferator-activated receptor-α (PPAR-α), with the features of composition and size of VLDL in an insulin-resistance rat model induced by a sucrose rich diet (SRD). Methods: The study was conducted on 12 male Wistar rats (180 g) receiving SRD (12 weeks) and 12 controls. Lipid profile, free fatty acids, glucose, and insulin were measured. Lipid content in liver and visceral fat were assessed. Isolated VLDL (d < 1.006 g/ml) was characterized by its chemical composition and size by HPLC. The respective hepatic expression of SREBP-1c and PPAR-α was determined (Western blot). Results: As expected, SRD had elevated triglycerides (TG), free fatty acids and insulin levels, and decreased HDL-cholesterol (p < 0.05), together with augmented hepatic and visceral fat (p < 0.05). SRD showed higher VLDL total mass - with increased TG content - and predominance of large VLDL (p < 0.05). SRD showed an increase in SREBP-1c (precursor and mature forms) and decreased PPAR-α expression (p < 0.045). SREBP-1c forms were positively associated with VLDL total mass (p < 0.04), VLDL-TG% (p < 0.019), and large VLDL% (p < 0.002). On the other hand, PPAR-α correlated negatively with VLDL total mass (p = 0.05), VLDL-TG% (p = 0.005), and large VLDL% (p = 0.002). Conclusions: Insulin-resistance, by coordinated activation of SREBP-1c and reduction of PPAR-α, could promote the secretion of larger and TG over-enriched VLDL particles, with greater atherogenic capacity

Introducción: En la insulinorresistencia, la VLDL presenta alteraciones que aumentan su potencial aterogénico. El mecanismo por el cual la insulinorresistencia promueve la producción de VLDL alteradas aún no se comprende completamente. Objetivo: evaluar la relación entre la expresión de la proteína ligadora de elementos reguladores de esteroles-1c (SREBP-1c) y de los receptores activados por factores de proliferación peroxisomal-α (PPAR-α) con las características de composición y tamaño de VLDL en un modelo animal de insulinorresistencia inducida por dieta rica en sacarosa (DRS). Métodos: Estudiamos 12 ratas macho Wistar (180 g) que recibieron DRS (12 semanas) y 12 controles. Se midieron el perfil lipídico, los ácidos grasos libres, la glucosa y la insulina. Se cuantificaron el contenido lipídico hapático y la grasa visceral. Se caracterizó la VLDL aislada (d < 1,006 g/ml) en composición química y tamaño (HPLC). Se determinó la expresión hepática de SREBP-1c y PPAR-α (Western-blot). Resultados: Esperadamente, el grupo DRS presentó elevación de triglicéridos (TG), ácidos grasos libres e insulina y disminución de colesterol-HDL (p < 0,05), junto con incremento de grasa hepática y visceral (p < 0,05). La DRS mostró una mayor masa total de VLDL —con mayor contenido de TG— y predominio de VLDL grandes (p < 0,05). DRS presentó expresión incrementada de SREBP-1c (precursor y maduro) y disminuida de PPAR-α (p < 0,045). Ambas formas de SREBP-1c se correlacionaron positivamente con masa total de VLDL (p < 0,04), TG%-VLDL (p < 0,019) y VLDL-grande % (p < 0,002). Mientras que PPAR-α se correlacionó negativamente con masa total de VLDL (p = 0,05), TG %-VLDL (p = 0,005) y VLDL-grande % (p = 0,002). Conclusiones: La insulinorresistencia, mediante una coordinada activación de SREBP-1c y reducción de PPAR-α, promovería la secreción de partículas de VLDL grandes y sobreenriquecidas en TG, con mayor capacidad aterogénica

From sugar to fat: How the transcription factor XBP1 regulates hepatic lipogenesis.

Lipogenesis occurs primarily in the liver, where dietary carbohydrates control the expression of key enzymes in glycolytic and lipogenic pathways. We have recently discovered that the transcription factor XBP1, best known as a key regulator of the unfolded protein response (UPR), is required for de novo fatty acid synthesis in the liver, a function unrelated to its role in the UPR.(1) XBP1 protein expression is induced in the liver by a high carbohydrate diet and directly controls the induction of critical genes involved in fatty acid synthesis. Specific deletion of XBP1 in adult liver using an inducible approach results in profound hypocholesterolemia and hypotriglyceridemia, which could be attributed to diminished production of lipids in the liver. Notably, this phenotype is not associated with fatty liver (hepatic steatosis) or significant compromise in protein secretion. XBP1 joins an already rich field of transcriptional regulatory proteins in the control of hepatic lipogenesis. Its function in lipogenesis appears to be highly significant as evidenced by the phenotype of the genetic mutant strain. A more complete understanding of the mechanisms by which XBP1 accelerates de novo fatty acid synthesis in the liver while preserving normal hepatic lipid composition is highly relevant to the treatment of diseases such as atherosclerosis and metabolic syndrome that are associated with dyslipidemia. Since excess fat accumulation in the liver could result from increased hepatic fatty acid synthesis, compounds that inhibit XBP1 activation may also be useful therapeutics for the treatment of human alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), increasingly common causes of morbidity and mortality in the United States.

Programmed cell death in fission yeast Schizosaccharomyces pombe.

Yeasts have proven to be invaluable, genetically tractable systems to study various fundamental biological processes including programmed cell death. Recent advances in the elucidation of the molecular pathways underlying apoptotic cell death in yeasts have revealed remarkable similarities to mammalian apoptosis at cellular, organelle and macromolecular levels, thus making a strong case for the relevance of yeast models of regulated cell death. Programmed cell death has been reported in fission yeast Schizosaccharomyces pombe, primarily in the contexts of perturbed intracellular lipid metabolism, defective DNA replication, improper mitotic entry, chronological and replicative aging. Here we review the current understanding of the programmed cell death in fission yeast, paying particular attention to lipid-induced cell death. We discuss our recent findings that fission yeast exhibits plasticity of apoptotic and non-apoptotic modes of cell death in response to different lipid stimuli and growth conditions, and that mitochondria, reactive oxygen species and novel cell death mediators including metacaspase Pca1, SpRad9 and Pck1 are involved in the lipotoxic cell death. We also present perspectives on how various aspects of the cell and molecular biology of this organism can be explored to shed light on the governing principles underlying lipid-mediated signaling and cell demise.

High plasma cholesteryl ester transfer protein levels may favour reduced incidence of cardiovascular events in men with low triglycerides.

AIMS: High cholesteryl ester transfer protein (CETP) concentrations are associated with increased risk of cardiovascular disease (CVD) in subjects with high triglycerides. We determined the relationship of plasma CETP with incident CVD in a population with relatively low triglycerides. METHODS AND RESULTS: A nested case-control study was performed in men participating in the prospective PREVEND study, after exclusion of CVD, diabetes mellitus, and lipid-lowering drugs use at baseline. Plasma CETP was measured in 111 men who developed a cardiovascular event (cases) during follow-up and in 116 controls who remained free of CVD. Fasting total cholesterol (P < 0.001) and triglycerides (P < 0.001) were higher, HDL cholesterol was lower (P = 0.001), but CETP was similar in cases and controls (P = 0.39). Cox proportional hazards regression analysis showed that CVD risk tended to be lower with higher plasma CETP after adjustment for age and lipids (hazard ratio 0.84; 95% CI 0.69-1.03, P = 0.10). Plasma CETP was lower in cases than in controls (P = 0.05) with triglycerides < or = 1.38 mmol/L (median), but not with higher triglycerides. The age-adjusted hazard ratio for CVD was 0.46 (95% CI 0.24-0.90) in men with triglycerides < or = 1.38 mmol/L and CETP > 2.26 mg/L (median) compared with men with similarly low triglycerides and CETP < or = 2.26 mg/L. With higher triglycerides, the hazard ratio for CVD was similar in both CETP categories. CONCLUSION: Relatively high plasma CETP may favour reduced CVD risk in the context of low triglycerides.

Abetalipoproteinemia in Israel: evidence for a founder mutation in the Ashkenazi Jewish population and a contiguous gene deletion in an Arab patient.

Abetalipoproteinemia (ABL) is a rare autosomal recessive metabolic disorder, characterized by the absence of plasma apolipoprotein B-containing lipoproteins and very low levels of plasma triglycerides and cholesterol. ABL is caused by mutations of the MTP gene. We investigated the genetic basis for ABL in a cohort of Israeli families. In Ashkenazi Jewish patients we identified a conserved haplotype and a common MTP mutation, p.G865X, with a carrier frequency of 1:131 in this population. We also report the first case of ABL and additional abnormalities in a Muslim Arab patient, due to a homozygous contiguous gene deletion of approximately 481 kb, including MTP and eight other genes.

Abundance of triacylglycerols in ganglia and their depletion in diabetic mice: implications for the role of altered triacylglycerols in diabetic neuropathy.

Herein, we report the first study on the mass distribution and molecular species composition of abundant triacylglycerols (TAG) in ganglia. This study demonstrates five novel findings. First, unanticipated high levels of TAG were present in all examined ganglia from multiple species (e.g. mouse, rat and rabbit). Second, ganglial TAG mass content is location-dependent. Third, the TAG mass levels in ganglia are species-specific. Fourth, dorsal root ganglial TAG mass levels in streptozotocin-induced diabetic mice are dramatically depleted relative to those found in untreated control mice. Fifth, mouse ganglial TAG mass levels decrease with age although molecular species composition is not changed. Collectively, these results indicate that TAG is an important component of ganglia and may potentially contribute to pathological alterations in peripheral neuronal function in diabetic neuropathy.

Serum lipid levels and in-hospital mortality in patients with intracerebral hemorrhage.

OBJECTIVE: To test the hypothesis that low serum cholesterol and low serum triglyceride levels at admission are related to an increase of in-hospital mortality in patients with first-ever supratentorial spontaneous intracerebral hemorrhage (ICH). METHODS: The authors obtained the serum cholesterol and triglyceride levels during the first 48 hours after first-ever ICH in 184 patients. They analyzed the impact of serum cholesterol and triglyceride concentrations on the in-hospital mortality after adjustment for possible confounding variables according to the results of the univariate analysis (age, hemorrhage volume, intraventricular extension, glycemia, serum albumin, and Glasgow Coma Scale score at admission) using the Cox proportional hazards model. They also analyzed the survival curves according to the cholesterol and triglyceride quartiles. RESULTS: Low serum cholesterol (p = 0.002; hazard ratio [HR] 0.988 [95% CI 0.979 to 0.997] mg/dL) and low serum triglyceride (p = 0.011; HR 0.986 [95% CI 0.976 to 0.997] mg/dL) concentrations were independently associated with increased in-hospital mortality after ICH. Analyzed by quartiles, the HR of in-hospital mortality was 3.136 (95% CI 0.833 to 11.087) for patients in the lowest cholesterol quartile (< 166 mg/dL) and 3.484 (95% CI 1.088 to 11.155) for patients in the lowest triglyceride quartile (< 74 mg/dL). CONCLUSIONS: Low serum cholesterol and triglyceride levels obtained during the first hours after intracerebral hemorrhage (ICH) are strong independent predictors of in-hospital mortality in patients with spontaneous supratentorial ICH.

Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease.

Epidemiological data indicate that low n-3 polyunsaturated fatty acids (PFA) intake is a readily manipulated dietary risk factor for Alzheimer's disease (AD). Studies in animals confirm the deleterious effect of n-3 PFA depletion on cognition and on dendritic scaffold proteins. Here, we show that in transgenic mice overexpressing the human AD gene APPswe (Tg2576), safflower oil-induced n-3 PFA deficiency caused a decrease in N-methyl-D-aspartate (NMDA) receptor subunits, NR2A and NR2B, in the cortex and hippocampus with no loss of the presynaptic markers, synaptophysin and synaptosomal-associated protein 25 (SNAP-25). n-3 PFA depletion also decreased the NR1 subunit in the hippocampus and Ca2+/calmodulin-dependent protein kinase (CaMKII) in the cortex of Tg2576 mice. These effects of dietary n-3 PFA deficiency were greatly amplified in Tg2576 mice compared to nontransgenic mice. Loss of the NR2B receptor subunit was not explained by changes in mRNA expression, but correlated with p85alpha phosphatidylinositol 3-kinase levels. Most interestingly, n-3 PFA deficiency dramatically increased levels of protein fragments, corresponding to caspase/calpain-cleaved fodrin and gelsolin in Tg2576 mice. This effect was minimal in nontransgenic mice suggesting that n-3 PFA depletion potentiated caspase activation in the Tg2576 mouse model of AD. Dietary supplementation with docosahexaenoic acid (DHA; 22 : 6n-3) partly protected from NMDA receptor subunit loss and accumulation of fodrin and gelsolin fragments but fully prevented CaMKII decrease. The marked effect of dietary n-3 PFA on NMDA receptors and caspase/calpain activation in the cortex of an animal model of AD provide new insights into how dietary essential fatty acids may influence cognition and AD risk.

Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids.

Male rat pups (21 days old) were placed on a diet deficient in n-3 polyunsaturated fatty acids (PUFAs) or on an n-3 PUFA adequate diet containing alpha-linolenic acid (alpha-LNA; 18 : 3n-3). After 15 weeks on a diet, [4,5-3H]docosahexaenoic acid (DHA; 22 : 6n-3) was injected into the right lateral cerebral ventricle, and the rats were killed at fixed times over a period of 60 days. Compared with the adequate diet, 15 weeks of n-3 PUFA deprivation reduced plasma DHA by 89% and brain DHA by 37%; these DHA concentrations did not change thereafter. In the n-3 PUFA adequate rats, DHA loss half-lives, calculated by plotting log10 (DHA radioactivity) against time after tracer injection, equaled 33 days in total brain phospholipid, 23 days in phosphatidylcholine, 32 days in phosphatidylethanolamine, 24 days in phosphatidylinositol and 58 days in phosphatidylserine; all had a decay slope significantly greater than 0 (p < 0.05). In the n-3 PUFA deprived rats, these half-lives were prolonged twofold or greater, and calculated rates of DHA loss from brain, Jout, were reduced. Mechanisms must exist in the adult rat brain to minimize DHA metabolic loss, and to do so even more effectively in the face of reduced n-3 PUFA availability for only 15 weeks.

Biochemical mechanism of lipid-induced impairment of glucose-stimulated insulin secretion and reversal with a malate analogue.

Hyperlipidemia appears to play an integral role in loss of glucose-stimulated insulin secretion (GSIS) in type 2 diabetes. This impairment can be simulated in vitro by chronic culture of 832/13 insulinoma cells with high concentrations of free fatty acids, or by study of lipid-laden islets from Zucker diabetic fatty rats. Here we show that impaired GSIS is not a simple result of saturation of lipid storage pathways, as adenovirus-mediated overexpression of a cytosolically localized variant of malonyl-CoA decarboxylase in either cellular model results in dramatic lowering of cellular triglyceride stores but no improvement in GSIS. Instead, the glucose-induced increment in "pyruvate cycling" activity (pyruvate exchange with tricarboxylic acid cycle intermediates measured by (13)C NMR), previously shown to play an important role in GSIS, is completely ablated in concert with profound suppression of GSIS in lipid-cultured 832/13 cells, whereas glucose oxidation is unaffected. Moreover, GSIS is partially restored in both lipid-cultured 832/13 cells and islets from Zucker diabetic fatty rats by addition of a membrane permeant ester of a pyruvate cycling intermediate (dimethyl malate). We conclude that chronic exposure of islet beta-cells to fatty acids grossly alters a mitochondrial pathway of pyruvate metabolism that is important for normal GSIS.

Schizosaccharomyces pombe cells deficient in triacylglycerols synthesis undergo apoptosis upon entry into the stationary phase.

Triacylglycerols (TAG) are important energy storage molecules for nearly all eukaryotic organisms. In this study, we found that two gene products (Plh1p and Dga1p) are responsible for the terminal step of TAG synthesis in the fission yeast Schizosaccharomyces pombe through two different mechanisms: Plh1p is a phospholipid diacylglycerol acyltransferase, whereas Dga1p is an acyl-CoA:diacylglycerol acyltransferase. Cells with both dga1+ and plh1+ deleted (DKO cells) lost viability upon entry into the stationary phase and demonstrated prominent apoptotic markers. Exponentially growing DKO cells also underwent dramatic apoptosis when briefly treated with diacylglycerols (DAGs) or free fatty acids. We provide strong evidence suggesting that DAG, not sphingolipids, mediates fatty acids-induced lipoapoptosis in yeast. Lastly, we show that generation of reactive oxygen species is essential to lipoapoptosis.

Triglyceride depletion in THP-1 cells alters cholesteryl ester physical state and cholesterol efflux.

To study macrophage lipid droplet composition and the effects of TG on cholesteryl ester (CE) physical state, hydrolysis, and cholesterol efflux, a technique was developed to remove the majority of accumulated TG with minimal effect on CE content. THP-1 macrophages were incubated with acetylated LDL, and the accumulated TG was depleted by incubation with the acyl-CoA synthetase inhibitor triacsin D in the presence of albumin. Before TG removal, all cellular lipid droplets were isotropic as determined by polarizing light microscopy. When the TG concentration was reduced, anisotropic lipid droplets were visible, indicating a change in physical state, and suggesting that TG and CE originally accumulated in mixed lipid droplets. This change in physical state of lipid droplets was associated with slower rates of CE hydrolysis and cholesterol efflux. Although lipid droplets within the same cell had a similar physical state after TG depletion, there was considerable variability among cells in the physical state of their lipid droplets. In conclusion, THP-1 macrophages store accumulated CE and TG in mixed droplets, and the proportion of CE to TG varies among cells. Reducing accumulated TG altered CE physical state, which in turn affected hydrolysis of CE and cholesterol efflux.

Acute fatty liver and HELLP syndrome: two distinct pregnancy disorders.

OBJECTIVE: to report the experience clinical, biochemical findings, complications and the maternal-perinatal outcome in patients with HELLP syndrome and acute fatty liver of pregnancy (AFLP) during the same period. MATERIALS AND METHODS: during the period between January 1996 and December 1999, medical records of patients with the discharge diagnosis of AFLP and HELLP syndrome were reviewed for presenting symptoms, laboratory findings, maternal and perinatal complications. Routine laboratory evaluation included serial measurement of liver function tests, complete blood cell count, coagulation profile and renal function tests. RESULTS: during the study period 10 patients had AFLP and 75 women had HELLP syndrome as the discharge diagnosis. Patients with HELLP syndrome had major parity than AFLP (P<0.006). The most common presenting symptom for patients with AFLP was malaise noted in all patients, nausea and/or vomiting, abdominal pain and jaundice were very common. Headache, abdominal or epigastric pain and hematuria were the most common symptoms of patients with HELLP syndrome. Women with AFLP had major hypoglycemia, hypocholesterolemia, hypotriglyceridemia, serum transaminase activity and low antithrombin III. Disseminated intravascular coagulation, acute renal insufficiency, ascites, seroma and encephalophaty were more common with AFLP. CONCLUSIONS: our opinion is that AFLP had clinical presentation, biochemical findings and complications clearly distinguished of HELLP syndrome.

Rhodococcus opacus strain PD630 as a new source of high-value single-cell oil? Isolation and characterization of triacylglycerols and other storage lipids.

The triacylglycerol (TAG)-accumulating, hydrocarbon-degrading bacterium Rhodococcus opacus strain PD630 and chemically induced storage-deficient mutants derived from this strain were investigated for their capability to accumulate storage lipids in the cytoplasm during cultivation under nitrogen-limiting conditions. Acylglycerols were analysed by matrix-associated laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) and by reversed-phase HPLC. Fatty acids comprising 13-19 carbon atoms in various acylglycerols constituted up to 76% of the cellular dry weight in gluconate-grown cells, with a significant proportion of odd-numbered fatty acids. Hydrolysis using pancreatic lipase and deacylation with ethyl magnesium bromide were employed to identify the stereospecific distribution of fatty acids at the glycerol. This analysis showed that the fatty acids were not randomly distributed between the three positions of the glycerol backbone. In comparison with common plant fats, where the longer and higher unsaturated fatty acids are predominantly found at position 2, R. opacus PD630 accumulated only the shorter and saturated fatty acids in this position. More than 100 mutants accumulating TAG at a significantly lower rate were obtained by chemical mutagenesis and identified by staining with Sudan Black B. All the mutants showed similar neutral lipid patterns by TLC analysis, with a small distinct spot exhibiting the same R(F) value as TAG; this was identified as a residual amount of TAG by preparative TLC and MALDI-TOF, indicating that this bacterium is possibly capable of synthesizing TAGs by at least two different pathways.

Establishment of a gene transfer system for Rhodococcus opacus PD630 based on electroporation and its application for recombinant biosynthesis of poly(3-hydroxyalkanoic acids).

A gene transfer system for Rhodococcus opacus PD630 based on electroporation was established and optimized employing the Escherichia coli-Rhodococcus shuttle vectors pNC9501 and pNC9503 as well as the E. coli-Corynebacterium glutamicum shuttle vector pJC1 as suitable cloning vectors for R. opacus PD630, resulting in transformation efficiencies up to 1.5 x 10(5) CFUs/microgram plasmid DNA. Applying the optimized electroporation protocol to the pNC9501-derivatives pAK68 and pAK71 harboring the entire PHB synthesis operon from Ralstonia eutropha and the PHA synthase gene phaC1 from Pseudomonas aeruginosa, respectively, recombinant PHA biosynthesis was established in R. opacus PD630 and the TAG-negative mutant ROM34. Plasmid pAK68 enabled synthesis and accumulation of poly(3HB) in R. opacus PD630 and ROM34 during cultivation under storage conditions from 1% (w/v) gluconate, of poly(3HB-co-3HV) from 0.2% (w/v) propionate and of poly(3HV) from 0.1% (w/v) valerate. Under storage conditions, recombinant strains of PD630 and ROM34 harboring pAK71 were able to synthesize and accumulate PHA of the medium chain length hydroxyalkanoic acids 3HHx, 3HO, 3HD and 3HDD from 0.1% (w/v) hexadecane or octadecane and a copolyester composed of 3HHp, 3HN and 3HUD from 0.1% (w/v) pentadecane or heptadecane. In the recombinant strains of PD630 and ROM34, the thiostrepton-induced overexpression of a 20 kDa protein was observed with its N-terminus exhibiting a homology of 60% identical amino acids to TipA from Streptomyces lividans.

Dislipidemias / Dyslipidemia

As doenças cardiovasculares representam a principal causa de óbito em indivíduos diabéticos. Entre os fatores que contribuem para que o processo aterosclerótico se revele mais extenso e severo nesses pacientes, podemos destacar as dislipidemias. O diabete melito pode levar a uma série de alterações no metabolismo lipídico. Aumento nos níveis de triglecerídeos, diminuiçäo dos níveis de HDL-colesterol e formaçäo de partículas de LDL-colesterol de maior potencial aterogênico representam as alterações mais comuns. As atuais recomendações visam a proporcionar diagnóstico e tratamento precoces. O diagnóstico envolve näo só a identificaçäo da dislipidemia em si, como também a investigaçäo de causas secundárias. A eficácia da terapêutica hipolipemiante exige a adesäo a mudançäs no estilo de vida e uso adequado de medicações.

Posibles efectos de una ingestion deficiente de grasa / Possibles effects of a deficient fat intake

Se senalan los posibles efectos de una dieta deficiente en grasa sobre la salud. Una dieta con poca cantidad de grasa hace dificil cubrir las necesidades de energia del cuerpo humano y ocasiona una disminucion de la actividad fisica espontanea, perdida progresiva de peso, cambios metabolicos adaptativos adicionales y alteraciones en la funcion reproductiva de lamujer y el crecimiento de los ninos. El acido linoleico y el acido a-linolenico, que deben ser suministrados imprescindiblemente por la dieta, tienen funciones energeticas y estructurales, y a partir de ellos se producen derivados que tienen sus mismas funciones; ademas, ellos son precursores de eicosanoides. La grasa de la dieta puede modificar la composicion de lipidos de las membranas celulares y esto, a su vez, alterar su fluidez y afectar sus funciones. La absorcion y utilizacion de antioxidantes liposolubles disminuyen con una ingestion baja de ggrasa. Por tanto, un acantidad insuficiente o una calidad inapropiada de grasa en la dieta puede afectar diversos procesos vitales y ser perjudicial para la salud

Posibles efectos de una ingestión deficiente de grasa / Possibles effects of a deficient fat intake

Se señalan los posibles efectos de una dieta deficiente en grasa sobre la salud. Una dieta con poca cantidad de grasa hace díficil cubrir las necesidades de energía del cuerpo humano y ocasiona una disminución de la actividad física espontánea, pérdida progresiva de peso, cambios metabólicos adaptativos adicionales y alteraciones en la función reproductiva de lamujer y el crecimiento de los niños. El ácido linoleico y el ácido Ó-linolénico, que deben ser suministrados imprescindiblemente por la dieta, tienen funciones energéticas y estructurales, y a partir de ellos se producen derivados que tienen sus mismas funciones; además, ellos son precursores de eicosanoides. La grasa de la dieta puede modificar la composición de lípidos de las membranas celulares y esto, a su vez, alterar su fluidez y afectar sus funciones. La absorción y utilización de antioxidantes liposolubles disminuyen con una ingestión baja de ggrasa. Por tanto, un acantidad insuficiente o una calidad inapropiada de grasa en la dieta puede afectar diversos procesos vitales y ser perjudicial para la salud (AU)