Fatty acid content and pattern of spleen phospholipids and triglycerides in normal and either type-1 or type-2 diabetic rats

The fatty acid pattern of spleen phospholipids and triglycerides was examined in fed or overnight fasted normal rats, streptozotocin-induced diabetic animals (type-1 diabetes) and Goto-Kakizaki rats (type-2 diabetes). In both phospholipids and triglycerides, differences were observed in the relative contribution of several fatty acids, as well as in the ratio between distinct fatty acids, when comparing fed to fasted rats, normal to diabetic animals and male to female Goto-Kakizaki rats. Diabetes increased to a greater extent the C22:6omega3 content of phospholipids in the spleen than in either the liver or the brain. However, the diabetes-induced changes in the C22:6omega3 content of triglycerides was closely comparable in the spleen, liver and brain. These findings suggest that the incorporation of fatty acids into triglycerides is controlled by comparable regulatory factor(s), e.g. insulinemia, in the spleen, liver and brain. In the case of phospholipids, however, an apparent adaptation to diabetic stress was more marked in the spleen than in the liver, and virtually absent in the brain. The proposed dichotomy in the environmental regulation of fatty acid synthesis and incorporation into phospholipids and triglycerides was further supported by distinct diabetes-related changes in the apparent activity of Delta9-desaturase in these two classes of lipids.     

Thalamic commissural connections in the cat

The high-affinity of [3H]gamma-aminobutyric acid (GABA) to GABAA receptors and [3H]baclofen to GABAB receptors were studied in the cerebellum of pyridoxine-deficient rats and compared to pyridoxine-supplemented controls. There was a significant increase in the maximal binding (Bmax) of both GABAA and GABAB receptors with no significant difference in their binding affinities (Kd). The changes observed suggest a supersensitivity of GABAA and GABAB receptors which seems to correlate negatively with the concentration of GABA in the cerebellum of pyridoxine-deficient rats.     

Brain phospholipid and triglyceride fatty acid content and pattern in Type 1 and Type 2 diabetic rats

The liver phospholipid and triglyceride content and/or fatty acid pattern differ(s) not solely in normal versus diabetic rats, but also in distinct rat models of diabetes mellitus. The present study reveals that a comparable situation prevails in the brain. Fed and overnight fasted female normal rats (N) and Goto-Kakizaki rats (GK), as well as fed rats rendered diabetic by a prior injection 3 days before sacrifice of streptozotocin (STZ) were examined. The brain phospholipid content, expressed as milligrams of fatty acids per gram wet weight, was comparable in all groups of rats, with an overall mean value of 31.2+/-0.8 (n=22). The GK rats differed from N and STZ rats by lower C18:0/C18:1omega9 and C18:2omega6/C18:3omega6 ratios and a lower C20:5omega3 content of brain phospholipids. The total amount of fatty acids in triglycerides was 7-8 times higher in GK than N and STZ rats. The GK rats differed from N and STZ rats by lower C16:0/C16:1omega7, C18:0/C18:1omega9 and (C16:0+C16:1omega7)/(C18:0+C18:1omega9) ratios in triglycerides. These findings extend to the brain, the knowledge of alterations in phospholipid and triglyceride content and/or fatty acid pattern in GK rats, as compared to N or STZ rats. The former rats indeed displayed: (i) an apparently increased activity of Delta9- and Delta6-desaturases, as suggested by the phospholipid measurements, and a decreased C20:5omega3 content in such phospholipids; (ii) a dramatic increase in brain triglyceride content; and (iii) an increased activity of Delta9-desaturase, as well as elongase, as judged from the triglyceride data.     

Effect of pyridoxine deficiency on the exploratory behavior of rats

Malnutrition early in life impairs the development of brain as well as behavior. In the present study the behavioral effects of preweaning pyridoxine deficiency in rats, as reflected by their exploratory score, have been investigated. The results clearly indicated that the body weight of pyridoxine-deficient rats was significantly less when compared to the control rats. Besides this, the sign of maturation of sensory perceptual mechanisms like the first day of eye opening and signs of maturation of neuromotor coordination like the day of supported standing are delayed in vitamin-deficient rats. The open-field activity reflected by the exploratory score was observed to be significantly less in vitamin-deficient rats. In short, considerable effects of prenatal pyridoxine deficiency were observed in the neonatal pups as stunting of growth and in the delayed onset of neuromotor coordination as well as a low level of open-field activity. The importance of maternal pyridoxine supplementation during pregnancy has been emphasized.     

Olfactory discrimination deficits in n-3 fatty acid-deficient rats

Docosahexaenoic acid (DHA), a long chain n-3 fatty acid, is present in high concentrations in the central nervous system. Although the role that DHA may play in neural function is not well understood, infants fed formulas containing low levels of n-3 fatty acids have decreased visual acuity and neurodevelopmental test scores. The present experiment assessed whether dietary manipulations that decrease the concentration of DHA in the brain interfered with olfactory-based learning. We fed rats a diet that provided adequate n-3 fatty acids or a diet that was deficient in n-3 fatty acids for two generations. The second generation n-3-deficient group had 81% less brain DHA (82% less in olfactory bulb) compared to the n-3-adequate group and made significantly more errors in a series of olfactory-cued, 2-odor discrimination tasks compared to the adequate group. These results suggest that lower levels of central nervous system DHA lead to poorer performance in a series of simple odor discrimination tasks.     

Unaltered brain membranes after prolonged intake of highly oxidizable long-chain fatty acids of the (n-3) series

Feeding rats a diet enriched in n-3 polyunsaturated fatty acids (Menhaden oil) increased the content in eicosapentaenoic acid 20:5 n-3 of brain phospholipids. Conversely 22:4 n-6 was reduced. These changes were not associated with alterations in either vitamin E concentration or glutathione peroxidase and catalase activities in cerebrum and cerebellum. No increase in peroxidative damage was found. Interestingly the major very-long-chain fatty acids (22:6 n-3 and 22:5 n-3) were not affected.     

Central nitric oxide inhibition modifies metabolic adjustments induced by exercise in rats

The influence of the central nervous system on metabolic function is of interest in situations deviating from basal states, such as during exercise. Our previous study in rats demonstrated that central nitric oxide (NO) blockade increases metabolic rate, reducing mechanical efficiency during exercise. To assess the role of brain nitric oxide in the plasma glucose, lactate and free fatty acids (FFAs) concentrations of rats submitted to an incremental exercise protocol on a treadmill until fatigue, 1.43 micromol (2 microl) of N(omega)-nitro-l-arginine methyl ester (L-NAME, n=6), a NO synthase inhibitor, or 2 microl of 0.15M NaCl (SAL, n=6) was injected into the lateral cerebral ventricle (icv) of male Wistar rats immediately before exercise (starting at 10 m/min, with increments of 1m/min every 3 min until fatigue, 10% inclination). Blood samples were collected through a chronic jugular catheter at rest and during exercise until fatigue. During exercise, the L-NAME-treated animals had the following metabolic response compared to controls: (1) an increased hyperglycemic response during the first 60% of time to fatigue; (2) higher plasma lactate levels; and (3) a significant transitory increase in plasma free fatty acids during the dynamic phase of exercise that returned to basal levels earlier than controls during the steady state phase of exercise. In addition L-NAME-treated rats fatigued earlier than controls. The data indicate that the inhibition of the brain nitrergic system induced by icv L-NAME treatment disrupted the accuracy of the neural mechanism that regulates plasma glucose and free fatty acids mobilization during exercise in rats.     

Effects of pyridoxine deficiency on rat intracellular cardiac action potentials

Summary Ventricular myocardial cell action potentials were measuredin situ by means of intracellular microelectrodes in the heart of pyridoxine-deficient rats both at spontaneous frequency and at frequencies increased to higher levels. Pyridoxine deficiency lowered the rates of depolarization and repolarization phases of ventricular action potentials thus lengthening their duration. A noticeable bradycardia seemed to be induced by pyridoxine deficiency.The modifications of ventricular action potentials and of frequency were coupled with a decrease of vitamin B₆ in the heart. Ventricular action potentials of pyridoxine-supplemented rats appeared to be largely restored to their normal parametes by pyridoxine administration. Pyridoxine-supplementation had also a remarkable effect upon frequency of the pyridoxine-deficient hearts since it reversed bradycardia to a striking tachycardia.This investigation was supported in part by research grant no. 04/130/5/3189 from Consiglio Nazionale delle Ricerche, Rome, Italy.     

The metabolic syndrome of fructose-fed rats: effects of long-chain polyunsaturated ω3 and ω6 fatty acids. II. Time course of changes in food intake, body weight, plasma glucose and insulin concentrations and insulin resistance

The time course for changes in food intake, body weight, plasma glucose and insulin concentrations and HOMA index was monitored over a period of 8 weeks in rats exposed from the 8th week after birth to diets containing either starch or fructose and sunflower oil. In two further groups of rats exposed to the fructose-rich diet part of the sunflower oil was substituted by either salmon oil rich in long-chain polyunsaturated ω3 fatty acids or safflower oil rich in long-chain polyunsaturated ω6 fatty acids. Despite lower food intake, the gain in body weight was higher in fructose-fed rats than in starch-fed rats. The supplementation of the fructose-rich diet by either ω3 or ω6 fatty acids lowered both food intake and body weight gain. The measurements of plasma glucose and insulin concentrations, HOMA index and insulinogenic index performed after overnight starvation were in fair agreement with those recorded at the occasion of an intraperitoneal glucose tolerance test, with higher values for plasma glucose concentration and HOMA index in the fructose-fed rats exposed to the sunflower oil (with or without enrichment with ω6 fatty acids) than in the starch-fed rats exposed to the sunflower oil or fructose-fed rats exposed to a diet enriched with ω3 fatty acids. Such was also the case for the measurements of glycated albumin at sacrifice. Moreover, the insulinogenic index was lower in the fructose-fed rats with or without dietary enrichment in ω6 fatty acids than in the fructose-fed rats with dietary enrichment in ω3 fatty acids. The elucidation of the biochemical determinants of the later difference requires further investigations in isolated pancreatic islets.     

Increased levels of lipid peroxides in aged rat brain as revealed by direct assay of peroxide values

Lipid peroxide concentrations in brain tissues of young and aged rats were determined by a direct method for measuring peroxide values. Three different brain regions were analyzed for lipid peroxides. The peroxide levels increased in all three regions of aged as compared to those of young rats, while lipid peroxides in plasma appeared to be stable along with age. Lipid peroxides in cerebrum and cerebellum increased 1.6-2.0 times in aged brains compared with young ones, and about 3-fold in the brain stem. Increased levels of lipid peroxides in aged brains seem not merely due to increased pools of precursor polyene fatty acids, but rather due to altered protection systems for lipid peroxidase formation.     

大豆异黄酮减轻反式脂肪酸诱导的大鼠动脉粥样硬化

目的观察大豆异黄酮减轻反式脂肪酸诱导的大鼠动脉粥样硬化的作用。方法将大鼠随机分为普通饲料组、反式脂肪酸组、大豆异黄酮组和反式脂肪酸+大豆异黄酮组,用试剂盒分别测量血中TG、HDL、LDL、IL-6和TNF-α的含量;培养牛主动脉内皮细胞,分为对照组、反式脂肪酸组和反式脂肪酸+大豆异黄酮组,Western blot法检测牛主动脉内皮细胞内NF-κB的磷酸化,同时检测细胞间黏附因子-1(ICAM-1)与血管细胞黏附因子(VCAM-1)蛋白表达。结果与普通饲料组比较,反式脂肪酸组血TG、LDL、IL-6和TNF-α明显升高(P0.05),HDL显著降低(P0.05)。大豆异黄酮干预后,血中TG、LDL、IL-6和TNF-α均降低(P0.01),HDL显著升高(P0.01)。大豆异黄酮能降低反式脂肪酸诱导的NF-κB磷酸化(P0.01);与对照组比较,大豆异黄酮能使反式脂肪酸诱导的ICAM-1和VCAM-1的表达降低(P0.01)。结论大豆异黄酮可减轻反式脂肪酸诱导的大鼠动脉粥样硬化作用。     

The maternal pheromone and deoxycholic acid in relation to brain myelin in the preweanling rat

We examined the lipid composition of blood and myelin in preweanling rats denied access to maternal feces. Levels of triglycerides and free fatty acids in the blood were reduced and in the brain the amount of myelin and the phospholipid concentration in myelin were also reduced. The addition of deoxycholic acid to ordinary laboratory chow prevented these deficiencies. We conclude that response to the maternal pheromone and the subsequent ingestion of deoxycholic acid through maternal feces promotes the deposition of normal brain myelin.     

Oral fish oil restores striatal dopamine release after traumatic brain injury

Omega-3 fatty acid administration can affect the release of neurotransmitters and reduce inflammation and oxidative stress, but its use in traumatic brain injury (TBI) has not been described extensively. We investigated the effect of 7 day oral fish oil treatment in the recovery of potassium evoked dopamine release after TBI. Sham rats and TBI rats were given either olive oil or fish oil by oral gavage and were subject to cerebral microdialysis. Olive oil treated TBI rats showed significant dopamine release deficit compared to sham rats, and this deficit was restored with oral fish oil treatment. There was no effect of fish oil treatment on extracellular levels of dopamine metabolites such as 3,4-dihydroxyphenylacetic acid and homovanillic acid. These results suggest the therapeutic potential of omega-3 fatty acids in restoring dopamine neurotransmission deficits after TBI.     

Effect of age on the modification of brain polyunsaturated fatty acids and enzyme activities by fish oil diet in rats

To determine the effect of age on the modification of brain lipids and functions by fish oil and lard diets, the polyunsaturated fatty acids, phospholipid states and enzyme activities of intracellular organelles in young and aged rats fed these diets were analyzed. The concentration of arachidonic acid (20:4) and docosahexaenoic acid (22:6) tended to decrease with increasing age. The UV absorption of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) also decreased. An increasing effect of the sardine oil diet on brain 22:6 concentration in aged rats was slightly greater than that in young rats. However, the modification of 20:4 concentration in aged rats was similar to that in young rats. Significant increases in the UV absorption of PE and PC of aged rats fed the fish oil diet were observed. The lactate dehydrogenase (LDH) activities of aged rats fed the sardine oil diet increased significantly, whereas the activities of aged rats fed the lard diet decreased. These results suggest that fish oil may be able to regulate the brain lipid composition and LDH activity in aged rats.     

Lipogenesis in the sand rat (Psammomys obesus)

Synthesis of fatty acids was measured in the liver and in epididymal adipose tissue of sand rats and albino rats. In chow-fed sand rats the rate of hepatic lipogenesis, as measured by the incorporation of 3H2O into fatty acids, was four- to sevenfold higher than in albino rats and in sand rats on a low-calorie saltbush diet. The contribution of [14C]glucose to lipogenesis in sand rat liver was lower than in albino rats. In fed sand rats lipogenesis incorporating 3H2O was stimulated by casein but not by glucose. In adipose tissue, lipogenesis measured 1 h after administration of 3H2O was much lower in sand rats than in albino rats. In vitro incorporation of [14C]glucose or acetate into adipose tissue fatty acids was negligible. In adipose tissue, uptake of very-low-density lipoproteins (VLDL) and lipoprotein lipase activity were sevenfold higher than in albino rats. Activities of NADP-malate dehydrogenase, acetyl CoA carboxylase, and fatty acid synthetase were considerably higher in the liver of chow-fed sand rats than in albino rats. It was concluded that obesity in sand rats originates from hepatic lipogenesis without a significant contribution of local fatty acid synthesis in adipose tissue.     

短链酰基辅酶A脱氢酶在大鼠心脏发育中的表达及其与心肌肥厚的关系

 目的：研究大鼠心脏发育过程中短链酰基辅酶A脱氢酶(short-chain acyl-CoA dehydrogenase, SCAD)的表达变化规律,并探讨其与高血压大鼠心肌肥厚的关系。方法：观察不同时期Wistar大鼠和不同周龄自发性高血压大鼠心肌组织的SCAD蛋白表达及酶活性变化,检测大鼠的血清和心肌游离脂肪酸含量。结果：与胚胎期19 d Wistar大鼠组比较,出生后1 d、2周、6周及16周龄Wistar大鼠组心肌的SCAD蛋白表达及酶活性增加,血清和心肌游离脂肪酸含量明显减少,二者之间呈负相关,其中,从2周龄Wistar大鼠组开始差异有统计学意义。与周龄匹配的WKY大鼠组比较,2周龄自发性高血压大鼠组收缩压尚未升高,6周龄及16周龄自发性高血压大鼠组收缩压显著增高;各时点自发性高血压大鼠组的左室重量指数均明显增高,提示自发性高血压大鼠在血压升高之前,已经发生了明显的心肌肥厚。与周龄匹配的WKY大鼠组比较,2周、6周及16周龄自发性高血压大鼠组心肌的SCAD蛋白表达及酶活性明显下降,血清和心肌游离脂肪酸含量明显增加,呈显著负相关。结论：(1)SCAD蛋白表达随大鼠心脏的生长发育逐渐上调,可能与心脏对脂肪酸的利用增加密切相关。(2)SCAD的蛋白表达及其酶活性显著下降, 可能是导致自发性高血压大鼠肥厚心肌能量代谢“胚胎型再演”的分子基础。     

Dopaminergic cell populations of the rat substantia nigra are differentially affected by essential fatty acid dietary restriction over two generations

Essential fatty acids play a crucial role in the activity of several neurotransmission systems, especially in the monoaminergic systems involved in cognitive and motor aspects of behavior. The present study investigated whether essential fatty acid dietary restriction over two generations could differentially affect dopaminergic cell populations located in the substantia nigra rostro-dorso-medial (SNrm) or caudo-ventro-lateral (SNcv) regions which display distinct neurochemical profile and vulnerability to lesions under selected pathological conditions. Wistar rats were raised from conception on control or experimental diets containing adequate or reduced levels of linoleic and α-linolenic fatty acids, respectively. Stereological methods were used to estimate both the number and soma size of tyrosine hydroxylase (TH)-immunoreactive neurons in the SNrm and SNcv. TH protein levels were assessed with Western blots. Long-term treatment with the experimental diet modified the fatty acid profile of midbrain phospholipids and significantly decreased TH protein levels in the ventral midbrain (3 fold), the number of TH-positive cells in the SNrm (～20%) and the soma size of these neurons in both SNrm (～20%) and SNcv (～10%). The results demonstrate for the first time a differential sensitivity of two substantia nigra dopaminergic cell populations to unbalanced levels of essential fatty acids, indicating a higher vulnerability of SNrm to the harmful effects induced by docosahexaenoic acid brain deficiency.     

Omega-3 fatty acids upregulate adult neurogenesis

Omega-3 fatty acids play crucial roles in the development and function of the central nervous system. These components, which must be obtained from dietary sources, have been implicated in a variety of neurodevelopmental and psychiatric disorders. Furthermore, the presence of omega-6 fatty acids may interfere with omega-3 fatty acid metabolism. The present study investigated whether changes in dietary ratios of omega-3:omega-6 fatty acids influence neurogenesis in the lobster (Homarus americanus) brain where, as in many vertebrate species, neurogenesis persists throughout life. The factors that regulate adult neurogenesis are highly conserved among species, and the crustacean brain has been successfully utilized as a model for investigating this process. In this study, lobsters were fed one of three diets that differed in fatty acid content. These animals were subsequently incubated in 5-bromo-2′-deoxyuridine (BrdU) to detect cells in S-phase of the cell cycle. A quantitative analysis of the resulting BrdU-labeled cells in the projection neuron cluster in the brain shows that short-term augmentation of dietary omega-3 relative to omega-6 fatty acids results in significant increases in the numbers of S phase cells, and that the circadian pattern of neurogenesis is also altered. It is proposed that the ratio of omega-3:omega-6 fatty acids may alter neurogenesis via modulatory influences on membrane proteins, cytokines and/or neurotrophins.     

Uptake and utilization of metabolites in specific brain sites relative to feeding status

Two experiments were conducted to assess potential alterations in fatty acid and glucose metabolism within specific brain sites in relation to the feeding status of the rat. An in vivo serial analysis of brain palmitate and glucose uptake demonstrated that hypothalamic uptake of these substrates was reciprocally altered with respect to satiety. Hypothalamic uptake of palmitate was increased by 300% and uptake of glucose was decreased by 30% in fasted compared with fed rats. Other regional differences were observed and discussed in the text. An in vitro analysis showed that hypothalamic fatty acid oxidation was affected by feeding status. The ventrolateral hypothalamus (VLH) of fasted rats had 45% greater rates of fatty acid oxidation than VLH of fed rats. No alterations were observed for VLH glucose oxidation and ventromedial hypothalamic glucose and fatty acid oxidation when comparing fed and fasted rats. Other brain sites did not show variance for glucose and fatty acid metabolism relative to feeding status. Fatty acid uptake and subsequent metabolism in the hypothalamus and other brain sites may be one component of food intake control and energy balance regulation.     

Modifications in cerebral lipid metabolism by severe glucose deprivation during aging

Severe glucose deprivation causes extensive derangement of phospholipids, fatty acids and free fatty acids in cerebral cortex of rats of different ages. The hypoglycemia-induced cerebral loss of phospholipids and fatty acids persists after 60 min recovery. Changes in individual classes of lipids are largely affected by aging. In fact, during glucose deprivation and recovery, in adult animals no preferential loss of polyunsaturated fatty acids and ethanolamine phosphoglycerides occurs, suggesting that the loss could be related to oxidative rather than to peroxidative degradation. On the contrary, in senescent rats the quoted events occur, suggesting the hypothesis of a possible peroxidation of cerebral lipids. Pretreatment with some agents is performed to elucidate the aging mode of action. Papaverine (acting on macrocirculation) is uneffective, while raubasine (acting on microcirculation and metabolism) and almitrine (acting on oxygen availability) interfere with the phospholipid and fatty acid metabolism, their action being different according to the rat age.