Alterations in lipid metabolism of spinal cord linked to amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons leading to muscle paralysis and death. While a link between dysregulated lipid metabolism and ALS has been proposed, lipidome alterations involved in disease progression are still understudied. Using a rodent model of ALS overexpressing mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A), we performed a comparative lipidomic analysis in motor cortex and spinal cord tissues of SOD1-G93A and WT rats at asymptomatic (~70 days) and symptomatic stages (~120 days). Interestingly, lipidome alterations in motor cortex were mostly related to age than ALS. In contrast, drastic changes were observed in spinal cord of SOD1-G93A 120d group, including decreased levels of cardiolipin and a 6-fold increase in several cholesteryl esters linked to polyunsaturated fatty acids. Consistent with previous studies, our findings suggest abnormal mitochondria in motor neurons and lipid droplets accumulation in aberrant astrocytes. Although the mechanism leading to cholesteryl esters accumulation remains to be established, we postulate a hypothetical model based on neuroprotection of polyunsaturated fatty acids into lipid droplets in response to increased oxidative stress. Implicated in the pathology of other neurodegenerative diseases, cholesteryl esters appear as attractive targets for further investigations.

Atorvastatin and Fenofibrate Increase the Content of Unsaturated Acyl Chains in HDL and Modify In Vivo Kinetics of HDL-Cholesteryl Esters in New Zealand White Rabbits.

Previous studies demonstrated modifications of high-density lipoproteins (HDL) structure and apolipoprotein (apo) A-I catabolism induced by the atorvastatin and fenofibrate combination. However, it remains unknown whether such structural and metabolic changes of HDL were related to an improvement of the HDL-cholesteryl esters (HDL-CE) metabolism. Therefore, we determined the structure of HDL and performed kinetic studies of HDL-CE radiolabeled with tritium in rabbits treated with atorvastatin, fenofibrate, and a combination of both drugs. The atorvastatin and fenofibrate combination increased the HDL size and the cholesterol and phospholipid plasma concentrations of the largest HDL subclasses. Moreover, the relative amount of unsaturated fatty acids contained in HDL increased, in detriment of saturated fatty acids as determined by gas chromatography-mass spectrometry. The transfers of cholesteryl esters (CE) from HDL to very low-density lipoproteins/low-density lipoproteins (VLDL/LDL) and vice versa were enhanced with atorvastatin, alone or in combination. Moreover, the direct elimination of CE from plasma via VLDL/LDL decreased with fenofibrate, whereas the direct elimination of CE via HDL augmented with the combination treatment. Taken together, the rise of unsaturated fatty acid content and the size increase of HDL, suggest that atorvastatin and fenofibrate induce more fluid HDL particles, which in turn favor an enhanced CE exchange between HDL and VLDL/LDL. Our results contribute to a better understanding of the relationship between the structure and function of HDL during the use of anti-dyslipidemic drugs.

Lipid levels in Biomphalaria glabrata infected with different doses of Echinostoma paraensei miracidia.

The effect of experimental exposure of Biomphalaria glabrata to different doses (5 and 50) of Echinostoma paraensei miracidia on the total levels of cholesterol and triglycerides circulating in the hemolymph and the neutral lipids in the digestive gland-gonad (DGG) complex were studied. The snails were dissected one, two, three and four weeks after infection to collect the hemolymph and DGG tissue, to measure the levels of cholesterol and triglycerides in the hemolymph and neutral lipids in the tissue. The results for the hemolymph showed a similar order of variation for both substrates tested in the first week after infection. The reduced levels of these lipids in the infected snails indicate intense use of these substrates both by the intermediate host and the parasite, suggesting its probable participation in the energy metabolism and structural construction of the developing larval stages. Alterations in the profile of neutral lipids in the DGG were also found. The results obtained indicate that in this model, the lipid metabolism depends on the miracidial dose used.

Leptin modulates nitric oxide production and lipid metabolism in human placenta.

Leptin has significant effects on appetite, energy expenditure, lipid mobilisation and reproduction. During pregnancy, leptin is produced in the placenta, a tissue in which leptin receptors are highly expressed, suggesting autocrine/paracrine functions for this hormone. In the present study, a putative role of leptin as a regulator of nitric oxide (NO) production and lipid metabolism was evaluated in term human placenta. We demonstrated that leptin enhanced NO production in human placental explants (P < 0.01). Although leptin did not modify the placental levels of cholesteryl esters and phospholipids, leptin decreased levels of triglycerides (P < 0.01) and cholesterol (P < 0.001) in term human placenta. The effect of leptin on lipid mass seems to be independent of the modulation of de novo lipid synthesis because leptin did not modify the incorporation of (14)C-acetate into any of the lipids evaluated. We investigated the effects of leptin on placental lipid catabolism and found that in both term human placental explants and primary cultures of trophoblastic cells, leptin increased glycerol release, an index of the hydrolysis of esterified lipids, in a dose-dependent manner. In conclusion, we have shown that leptin affects NO production and lipid catabolism in human placenta, providing supportive evidence for a role of leptin in placental functions that would determine the transfer of nutrients to the developing fetus.

Dietary fat saturation produces lipid modifications in peritoneal macrophages of mouse.

We investigated the effects of a saturated fat diet on mice lipid metabolism in resident peritoneal macrophages. Male C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet, containing coconut oil (COCO diet), or the control diet, containing soybean oil as fat source. Fat content of each diet was 15% (w/w). Mice were fed for 6 weeks until sacrifice. In plasma of mice fed the COCO diet, the concentration of triglyceride, total cholesterol, HLD- and (LDL+VLDL)-cholesterol, and thiobarbituric acid-reactive substances (TBARS) increased, without changes in phospholipid concentration, compared with the controls. In macrophages of COCO-fed mice, the concentration of total (TC), free and esterified cholesterol, triglyceride, phospholipid (P) and TBARS increased, while the TC/P ratio did not change. The phospholipid compositions showed an increase of phosphatidylcholine and phosphatidylserine + phosphadytilinositol, a decrease of phosphatidylethanolamine, and no change in phosphatidylglycerol. (3)H(2)O incorporation into triglyceride and phospholipid fractions of macrophages increased, while its incorporation into free cholesterol decreased. Incorporation of [(3)H]cholesterol into macrophages of COCO-fed mice and the fraction of [(3)H]cholesterol ester increased. COCO diet produced an increase in myrystic, palmitic and palmitoleic acids proportion, a decrease in linoleic and arachidonic acids and no changes in stearic and oleic acids, compared with the control. Also, a higher relative percentage of saturated fatty acid and a decrease in unsaturation index (p <0.001) were observed in macrophages of COCO-fed mice. These results indicate that the COCO-diet, high in saturated fatty acids, alters the lipid metabolism and fatty acid composition of macrophages and produces a significant degree of oxidative stress.

Lipid metabolism in the embryos of diabetic rats during early organogenesis: modulatory effect of prostaglandin E2.

The purpose of this work was to evaluate de novo lipid biosynthesis and the lipid profile, and to study the effect of prostaglandin E2 (PGE2; prostaglandin has previously been found to be involved in diabetes embryopathy) on lipid metabolism in embryos from control and streptozotocin-induced diabetic rats during organogenesis. Increased levels of triacylglycerols were found in embryos of diabetic rats compared with controls, whereas no differences were detected in the levels of cholesterol, cholesterylester, phosphatidylcholine and phosphatidylethanolamine. When the de novo synthesis of lipids in the embryo was studied using [14C]acetate as a tracer, a diminished rate of incorporation of [14C]acetate into the evaluated lipid classes was detected in the diabetic embryo compared with controls. Addition of PGE2 did not modify the incorporation of [14C]acetate into any of the lipid species of control embryos, but enhanced the incorporation of [14C]acetate into triacylglycerol, cholesterylesters, phosphatidylcholine and phosphatidylethanolamine of embryos from diabetic rats. The study's results show alterations in both synthesis and concentrations of lipids in the embryos of diabetic rats. Interestingly, the results demonstrate that the addition of PGE2, a prostaglandin that reverses the embryonic morphological abnormalities induced by diabetes, prevents disturbances in embryo lipid synthesis caused by diabetes.

Manipulación dietaria de la composición de ácidos grasos de los ésteres de colesterol en el hígado de rata y su efecto sobre las lipoproteínas del plasma / Dietary manipulation of the fatty acids composition of the cholesterol esters in the rat liver and its effect on the plasm lipoproteins

Se conocen las relaciones entre los ácidos grasos dietarios, la aterogénesis y las concentraciones de lípidos del plasma. Puesto que las lipoproteínas del plasma en parte provienen del hígado, es de interés identificar como los ácidos grasos de la dieta influyen sobre los lípidos del hígado. Investigamos en la rata el efecto de modificaciones de los ácidos grasos dietéticos sobre el hígado de ratas machos. Los animales se sometieron a dietas con igual contenido de grasa total, pero provenientes de tres fuentes distintas: aceite de pescado, maíz y palma. En el primero hay una proporción importante de ácidos grasos poliinsaturados de la serie n-3, en el segundo predominan los ácidos grasos de la serie n-6 y en el tercero los ácidos oleico y el palmítico. Es bien claro que la modificación principal recae sobre los ésteres del colesterol hepático, sus ácidos grasos y las concentraciones de las lipoproteínas del plasma

Changes in lipid composition during metamorphosis of bonefish (Albula sp.) leptocephali.

During metamorphosis of bonefish (Albula sp.) larvae (leptocephali) all energy requirements are provided by breakdown of endogenous compounds, with lipid catabolism accounting for about 80% of total energy production. The principal objective of the present study was to characterize the lipid classes and fatty acids utilized. Analysis of whole-body lipid content indicated that larvae lost about half (3.6 mg) of their total lipid during the 10-d period. Percentages of neutral and polar lipid in early metamorphosing larvae were 64.2 and 35.8%, respectively; these values showed little change during metamorphosis, indicating that both lipid classes were catabolized. Triacylglycerols, the principal neutral lipid of all metamorphic stages, decreased by 1.8 mg, accounting for half of the decrease in total lipid. Levels of phosphatidylethanolamine, the principal polar lipid in early larvae, decreased by more than 50% during metamorphosis; levels of phosphatidylcholine, which was not detected in early larvae, increased. Fatty acids showing the largest net decreases, presumedly used as energy sources, were 16:0 (30.4%), 14:0 (13.8%), 16:1n-7 (12.2%), 20:5n-3 (7.7%), 18:1n-9 (7.4%), and 18:4n-3 (6.9%). Most of 22:6n-3, the second most abundant fatty acid of early larvae, was conserved.

Indicators of long chain polyunsaturated fatty acid status of exclusively breastfed infants at delivery and after 20-22 days

The fatty acid composition of plasma cholesterol esters (CE), erythrocytes (RBC) and mature milk from seven lactating women and their exclusively breastfed newborns, living on Dominica, were studied. Blood samples were taken from umbilical cord and mother at birth. A sample of breastmilk was collected on day 20-22 postpartum, together with a blood sample from the baby. At birth, cord blood plasma CE and RBC total long chain polyunsaturated fatty acid (LC-PUFA) contents were higher, and linoleic (18:2c, omega 6) and alpha-linolenic (18:3c, omega 3) acid contents lower, than in corresponding maternal compartments. Cord blood RBC LC-PUFA omega 3 content was lower and LC-PUFA omega 6 content higher than in maternal RBC. After birth, feeding with human milk led to a drop in LC-PUFA content in the plasma CE fraction, whereas RBC LC-PUFA content remained virtually constant. Current understanding of the origin and relative affinity of fatty acids incorporated in plasma CE and RBC suggests that RBC LC-PUFA content is a more reliable parameter for LC-PUFA status than plasma CE LC-PUFA content. The RBC LC-PUFA data suggest therefore that at birth the newborn has a lower LC-PUFA omega 3 status than the mother, and that this does not change during three weeks of exclusive breastfeeding (AU)

[Cholesterol and phospholipids in human seminal plasma before and after vasectomy]. / Colesterol y fosfolípidos en el plasma seminal humano antes y después de vasectomía.

Before and 2.6 months after vasectomy the alterations of secretory capacity and physiologic damage of the accessory genital glands, were evaluated by means of chemical analyses of certain constituents of seminal plasma such as free cholesterol, esterified cholesterol and phospholipids. The results of these studies showed that the ratio between the concentration of free cholesterol and esterified cholesterol is constant six months after vasectomy and the concentration of phospholipids decreases two months after vasectomy. These results are significant and may be important to know the alterations of secretory capacity of the human genital glands after vasectomy.

PIP: 38 men who had undergone vasectomy for fertility regulation had 3 semen samples taken before and 2 and 6 months after the operation in order to determine the concentration of cholesterol and phospholipids in the seminal plasma for the evaluation of any possible changes in the physiology of genital glands. Prior to vasectomy there were 130 +or- 50 million of spermatozoa/ml of ejaculate with a 75% +or- 11% motility in a sample of 35 men. There was no statistically significant change in cholesterol content before and 2 and 6 months after vasectomy, nor was there a significant difference between free cholesterol and esterified cholesterol. This indicated good correspondence in the content of glandular secretions of the male genital tract, mainly the prostate and the seminal vesicles. On the other hand, the concentration of phospholipids diminished 2 and 6 months after vasectomy from 230 +or- 90 mcg moles/in 21 patients to 100 +or- and 100 +or- 20 mcg moles/1 in 15 patients, respectively. There was no significant difference in the average volume of seminal plasma 2 and 6 months after vasectomy. The decrease of the phospholipid content could be attributed to the inhibition of the biosynthesis of phospholipids owing to the hypertrophy of the epididymis or the absence of phospholipid secretion originating from the testicular fluid. Not all alterations in genital glands are apparent immediately, therefore time is an important parameter in the evaluation of the response of the organism to vasectomy.