Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids

2005 ◽  
Vol 98 (3) ◽  
pp. 981-990 ◽  
Author(s):  
Eric D. Bruder ◽  
Ping C. Lee ◽  
Hershel Raff

Dexamethasone is used as treatment for a variety of neonatal syndromes, including respiratory distress. The present study utilized the power of comprehensive lipid profiling to characterize changes in lipid metabolism in the neonatal lung and brain associated with dexamethasone treatment and also determined the interaction of dexamethasone with hypoxia. A 4-day tapering-dose regimen of dexamethasone was administered at 0800 on postnatal days 3 (0.5 mg/kg), 4 (0.25 mg/kg), 5 (0.125 mg/kg), and 6 (0.05 mg/kg). A subgroup of rats was exposed to hypoxia from birth to 7 days of age. Dexamethasone treatment elicited numerous specific changes in the lipid profile of the normoxic lung, such as increased concentrations of saturated fatty acids in the phosphatidylcholine and cholesterol ester classes. These increases were more profound in the lungs of hypoxic pups. Additional increases in cardiolipin concentrations were also measured in lungs of hypoxic pups treated with dexamethasone. We measured widespread increases in serum lipids after dexamethasone treatment, but the effects were not equivalent between normoxic and hypoxic pups. Dexamethasone treatment in hypoxic pups increased 20:4n6 and 22:6n3 concentrations in the free fatty acid class of the brain. Our results suggest that dexamethasone treatment in neonates elicits specific changes in lung lipid metabolism associated with surfactant production, independent of changes in serum lipids. These findings illustrate the benefits of dexamethasone on lung function but also raise the potential for negative effects due to hyperlipidemia and subtle changes in brain lipid metabolism.

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4112-4112
Author(s):  
Lisa J Robinson ◽  
Janelle R Zacherl ◽  
Stephanie J Mihalik ◽  
Irina L. Tourkova ◽  
Claudette M St Croix ◽  
...  

Abstract Atherosclerosis, through its sequelae of heart disease, stroke and peripheral vascular disease, underlies substantial human morbidity and mortality. The incidence of atherosclerosis increased markedly over the last century paralleling the increase in fat, particularly saturated fat, in the modern diet. Furthermore, artificial hydrogenation of saturated fats, originally introduced to provide a ‘healthier’ dietary substitute, resulted in consumption of non-physiological trans fatty acids that are themselves now strongly linked to the development of atherosclerosis. A major cellular target for the negative effects of fatty acids in the vasculature appears to be the macrophage, which through actions including the production of inflammatory cytokines, plays a central role of the pathophysiology of atherosclerosis. Despite the importance of these effects, our understanding of the fundamental molecular changes that underlie the negative effects of fatty acids, and especially trans fatty acids, remains fragmentary. In previous work we showed that prolonged exposure of human macrophages to the 18 carbon trans-monoenoic fatty acid elaidic acid impaired lipid metabolism, partially blocking beta-oxidation and thereby altering cellular lipid composition. To determine the functional consequences of this alteration in cellular lipids, we next examined changes in macrophage gene expression. Primary human macrophages derived from peripheral blood monocytes were treated with the cis fatty acid oleate or the trans fat elaidate for 44 hours, and gene expression was evaluated using the affymetrix gene array, with significant differences confirmed by real time quantitative PCR. Expression of genes linked directly to lipid metabolism differed, as expected, but the most striking differences between cis and trans fatty acid treated macrophages were in their expression of regulators of zinc homeostasis. In particular, there was a marked divergence in expression levels for metallothioneins, the zinc binding proteins which regulate intracellular zinc levels: metallothionein expression was consistently lower in the elaidate-treated macrophages. In contrast, the zinc transporter SLC39A10 was significantly upregulated in macrophages by exposure to the trans but not the cis fatty acid. SLC39A10 mediates uptake of extracellular zinc by cells and its release from organellar stores; its effects are opposed by SLC30, which export zinc from the cytosol but were not induced by exposure to elaidate. These results suggested that trans fats would increase zinc activity in macrophages. To test this we used the fluorescent zinc indicator FluoZin3 (N-(carboxymethyl)-N-[2-[2-[2(carboxymethyl)amino]-5-(2,7,-difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)phenoxy]ethoxy]-4-methoxyphenyl]glycine). These studies confirmed that macrophages exposed to elaidate showed increased intracellular Zn2+, compared to both untreated or oleate-treated macrophages. Furthermore, the increase in zinc activity was associated with activation of the NFkB signaling pathway: macrophages treated with elaidic acid showed prominent nuclear translocation of NFkB p65, and the effect was abrogated by cotreatment with the zinc chelator TPEN. We next compared the effects of the trans fat with those of saturated fatty acids. Macrophages exposed to stearate or palmitate showed a milder and delayed increase in metallothionein expression, compared to those treated with oleate, but, like oleate, stearate and palmitate had no effect on the expression of zinc transporters. Studies using FluoZin3 showed a mild early increase in cytosolic Zn2+ following stearate or palmitate treatment, but at the later time points, when metallothionein expression was increased by the saturated fatty acids as well as by oleate, zinc activity returned to baseline. Only elaidic acid, which upregulated the zinc transporter, produced a sustained increase in intracellular macrophage Zn2+. Stearate and palmitate also stimulated early translocation of NFkB to the nucleus. These results suggest that trans fatty acids, while mimicking some activation pathways stimulated by the saturated fatty acids, exert distinct effects through sustained alterations in zinc regulatory proteins that promote elevated intracellular Zn2+. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kapil Dev ◽  
Jubeda Begum ◽  
Avishek Biswas ◽  
Nasir Akbar Mir ◽  
Jitendra Singh ◽  
...  

AbstractThis study investigated the role of dietary prebiotic mannan-oligosaccharides (MOS), and probiotic Bifidobacterium bifidum (BFD) in lipid metabolism, deposition, and consequent health indices in broiler chicken. The supplementation of 0.2% MOS along with either 106 or 107 CFU BFD/g feed resulted in downregulation of Acetyl-CoA carboxylase, fatty acid synthase, sterolregulatory element binding protein-1, and apolipoprotein B100; and up-regulation of peroxisome proliferator activated receptor-α AMP-activated protein kinase α-1, and stearoyl CoA (∆9) desaturase-1 hepatic expression in broiler chicken. The birds supplemented with 0.2% MOS along with either 106 or 107 CFU BFD/g feed depicted lower body fat percentage, palmitic acid, stearic acid, and saturated fatty acid contents, whereas, higher palmitoleic acid, oleic acid, and MUFA contents were observed. The ∆9-desaturase indices of chicken meat have shown higher values; and elongase index (only thigh) and thioesterase index have shown lower values in birds supplemented with 0.2% MOS along with either 106 or 107 CFU BFD/g feed. The meat health indices such as Polyunsaturated fatty acids (PUFA)/Saturated fatty acids (SFA) ratio, Mono-saturated fatty acids (MUFA)/SFA ratio, unsaturated fatty acids (UFA)/SFA ratio, hypocholesterolemic/hypercholesterolemic fatty acid ratio, saturation index, atherogenic index, thrombogenic index, and hypercholesterolemic fatty acid content were positively improved in birds supplemented with 0.2% MOS along with either 106 or 107 CFU BFD/g feed. Similarly, the birds supplemented with 0.2% MOS along with either 106 or 107 CFU BFD/g feed have shown lower serum triglyceride and total cholesterol levels along with higher high density levels and improved serum health indices cardiac risk ratio, atherogenic coefficient, and, atherogenic index of plasma.


1981 ◽  
Vol 59 (3) ◽  
pp. 208-219 ◽  
Author(s):  
Ming-Jarm Lau ◽  
Kevin M. W. Keough

The phospholipids of lung and lung lavage fluid from map turtles (Malaclemys geographica) acclimated to 5, 14, 22, and 32 °C have been analyzed. The yield of surfactant (lavage) lipid P was higher at 32 than at 5 °C, but there was no significant change in lung lipid P. The relative proportions of phospholipids from the lung were PC > PE > SM > PS > PI, while those for the lavage were [Formula: see text]. PC constituted 71–78% of the surfactant phospholipid over the temperature range. Small changes in the amounts of PC and PE of lung and in PC and PI of lavage were observed at different temperatures. The fatty acid compositions of the lipids from the two sources were different in many respects. The lavage lipids contained more saturated acids, especially palmitic acid, than did the lung lipids. The fatty acid compositions indicated the presence of disaturated PC in lung lavage and diunsaturated species of PC and PE in lung. The total saturated fatty acids of PC and PE in lung and of PC in surfactant increased at higher temperatures. In the surfactant PC this increase reflected principally a rise in palmitate and a drop in palmitoleate contents. The saturated PC obtained from lavage at each temperature contained more than 85% palmitic acid, indicating that the principal saturated PC was DPPC. These changes are consistent with the type of alterations in the lipid compositions of membranes which occur during homeoviscous adaptation.


1998 ◽  
Vol 79 (5) ◽  
pp. 419-424 ◽  
Author(s):  
Helen M. Roche ◽  
Antonis Zampelas ◽  
Kim G. Jackson ◽  
Christine M. Williams ◽  
Michael J. Gibney

Epidemiological evidence shows that a diet high in monounsaturated fatty acids (MUFA) but low in saturated fatty acids (SFA) is associated with reduced risk of CHD. The hypocholesterolaemic effect of MUFA is known but there has been little research on the effect of test meal MUFA and SFA composition on postprandial lipid metabolism. The present study investigated the effect of meals containing different proportions of MUFA and SFA on postprandial triacylglycerol and non-esterified fatty acid (NEFA) metabolism. Thirty healthy male volunteers consumed three meals containing equal amounts of fat (40g), but different proportions of MUFA (12, 17 and 24% energy) in random order. Postprandial plasma triacylglycerol, apolipoprotein B-48, cholesterol, HDL-cholesterol, glucose and insulin concentrations and lipoprotein lipase (EC 3.1.1.34) activity were not significantly different following the three meals which varied in their levels of SFA and MUFA. There was a significant difference in the postprandial NEFA response between meals. The incremental area under the curve of postprandial plasma NEFA concentrations was significantly (P = 0·03) lower following the high-MUFA meal. Regression analysis showed that the non-significant difference in fasting NEFA concentrations was the most important factor determining difference between meals, and that the test meal MUFA content had only a minor effect. In conclusion, varying the levels of MUFA and SFA in test meals has little or no effect on postprandial lipid metabolism.


2020 ◽  
Author(s):  
Nasir Akbar Mir ◽  
Praveen K. Tyagi ◽  
Jubeda Begum ◽  
Kapil Dev ◽  
Avishek Biswas ◽  
...  

Abstract Background:Flaxseed in a richest terrestrial source of w-3 fatty acid – alpha-linolenic acid (ALA) which can be incorporated in chicken meat when it is included in chicken ration. ALA can further be acted up on by desaturating enzymes to generate PUFA such as EPA and DHA which increase the health value of chicken meat. However, dietary flaxseed results in concurrent increase in lipid oxidation due higher unsaturation and negative impact on chicken growth performance. These negative effects of flaxseed feeding can be reversed by chromium supplementation in broiler chicken. Thus, this study investigated growth performance and efficiency, lipid composition, lipid metabolism, health indices, and serum lipid chemistry of broiler chicken fed flaxseed meal (FSM) and chromium (Cr).Results:Feeding of 100 g FSM exerted negative effects on the growth performance during starter phase only (0-3 weeks) and overall growth efficiency parameters in broiler chicken, whereas, Cr supplementation reversed these negative effects.100 g FSM reduced abdominal fat in chicken and Cr supplementation linearly decreased it with minimum at 1.5 mg Cr/kg diet.Feeding of 100 g FSM favourably improved the activities of lipid metabolism enzymes which resulted in improved fatty acid profile and health indices of chicken meat.No significant effect of Cr supplementation was observed on lipid metabolism, fatty acid profile, and health indices of chicken meat.100 g FSM decreased serum total cholesterol, triglyceride, cardiac risk ratio, atherogenic coefficient, and atherogenic index of plasma, whereas, Cr supplementation decreased these parameters linearly with increasing levels. Antioxidant enzyme activities and lipid peroxidation were increased by FSM, whereas, Cr supplementation linearly decreased them with increasing levels; and inverse trend was observed in serum HDL cholesterol levels.Conclusions: Feeding of 100 g FSM exert negative effects on growth performance of young chicken (0-3 weeks), favourably alter lipid metabolism which results in improved fatty acid profile and health indices of chicken meat. It improves the serum lipid profile and atherogenic indices in broiler chicken, but negatively affects the oxidative stability of lipids. However, Cr supplementation at the rate of 1.5 mg/kg diet successfully overcomes these negative effects of FSM feeding on growth performance and lipid oxidative stability.


2020 ◽  
Vol 48 (08) ◽  
pp. 1841-1858
Author(s):  
Joonwoo Park ◽  
KeunOh Choi ◽  
Jeonggeun Lee ◽  
Jong-Min Jung ◽  
YoungJoo Lee

Bisphenol A (BPA), which is known to be an endocrine-disrupting chemical (EDC), is associated not only with estrogen activity and reproductive toxicity but also with a variety of metabolic disorders. BPA affects glucose tolerance, cholesterol biosynthesis, and fatty acid synthesis. Ginseng is a traditional medicinal plant that has been widely used in East Asia for more than 2000 years, and a number of health effects have been reported. Korean Red Ginseng (KRG) has also been shown to have effects on lipid metabolism and body weight reduction in vivo in obese mice. In this study, we administered BPA and KRG to ovariectomized (OVX) ICR mice. BPA (800 mg/kg/day) and KRG (1.2 g/kg/day) were orally administered to OVX mice for 3 days. KRG inhibited the increase in total fatty acid level by BPA as determined by lipid profiling in the liver of OVX mice. In addition, transcriptome analysis showed that KRG inhibited BPA-induced changes in lipid metabolic process-related genes. Our findings suggest that KRG can regulate BPA-induced changes in lipid metabolism.


2020 ◽  
Vol 21 (9) ◽  
pp. 3183
Author(s):  
Olaia Urrutia ◽  
José Antonio Mendizabal ◽  
Leopoldo Alfonso ◽  
Beatriz Soret ◽  
Kizkitza Insausti ◽  
...  

Dietary recommendations by health authorities have been advising of the importance of diminishing saturated fatty acids (SFA) consumption and replacing them by polyunsaturated fatty acids (PUFA), particularly omega-3. Therefore, there have been efforts to enhance food fatty acid profiles, helping them to meet human nutritional recommendations. Ruminant meat is the major dietary conjugated linoleic acid (CLA) source, but it also contains SFA at relatively high proportions, deriving from ruminal biohydrogenation of PUFA. Additionally, lipid metabolism in ruminants may differ from other species. Recent research has aimed to modify the fatty acid profile of meat, and other animal products. This review summarizes dietary strategies based on the n-3 PUFA supplementation of ruminant diets and their effects on meat fatty acid composition. Additionally, the role of n-3 PUFA in adipose tissue (AT) development and in the expression of key genes involved in adipogenesis and lipid metabolism is discussed. It has been demonstrated that linseed supplementation leads to an increase in α-linolenic acid (ALA) and eicosapentaenoic acid (EPA), but not in docosahexaenoic acid (DHA), whilst fish oil and algae increase DHA content. Dietary PUFA can alter AT adiposity and modulate lipid metabolism genes expression, although further research is required to clarify the underlying mechanism.


2018 ◽  
Vol 46 (1) ◽  
pp. 10 ◽  
Author(s):  
Anderson Elias Bianchi ◽  
Talyta Zortea ◽  
Chrystian Jassana Cazzarotto ◽  
Gustavo Machado ◽  
Luis Gustavo Pellegrini ◽  
...  

Background: Sheep milk production is becoming an important alternative in the agricultural sector. It is used principally to produce fine cheeses, yogurts, and ice creams, and these produced from sheep’s milk are beneficial to human health. Previous study with palm oil shows increase in fat levels in sheep’s milk. Our hypothesis for increased fat in milk is that palm oil increases lipid metabolism as well as tissue reserves. Sheep consuming this palm oil will have a change in the fatty acid profile of milk, increasing levels of unsaturated fatty acids. Therefore, the aim of this study was to determine the levels of cholesterol and triglycerides, as well as fatty acid profile of milk these ewes fed of palm oil.Materials, Methods & Results: Thirty-six lactating sheep were divided in four groups (n = 9), with each group receiving various concentrations of palm oil in diet (0%, 2%, 4%, and 6% which corresponds to T 0, 2, 4 and 6, respectively). The diets in each treatment were isoproteic and isoenergetic. The experiment lasted 120 days, and blood and milk samples were collected on days 60 and 12 of the experiment. Blood was collected for seric analysis of lipid metabolism. Was collected milk samples and analyzed the content of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA). An increase (P < 0.05) in triglyceride and coleterol levels in the serum of the animals that received the highest concentrations of palm oil in the diet (T4 and T6). The centesimal composition of fat, lactose, and protein in milk was not different at days 60 and 120 (P > 0.05) between groups, but numerically the animals in T4 and T6 had higher percentage of fat in milk. A decrease in milk SFA levels was observed on day 120 at T6. There was a significant reduction in caproic acid, caprylic acid, hendecanoic acid, lauric acid, and pentadecyl acid. The levels of palmitic acid (C16:0) increased when compared with the control group. Also at 150 days, it was observed a reduction in the percentage of area capric acid and myristic acid in animals that had higher doses of calcium salts in the diet, different from stearic acid, which increased. A variability in MUFA levels was observed during the evaluated periods, i.e. heptadecenoic acid decreased on days 60 and 120 for animals of T6; an increased content of elaidic acid was observed on day 60, and levels of vaccenic acid decreased on day 120 at 6% palm oil. A decrease in PUFA levels was observed on day 60 at T6, specifically a significant reduction in alpha-linolenic and arachidonic acid, as well as levels of conjugated linoleic acid 1 decreased on day 120 for animals supplemented with 6% of palm oil.Discussion: The addition of plama oil in the diet of dairy sheep increased seric levels of triglycerides and cholesterol, as well as positively altered the composition of fatty acids in milk, making a product healthier to the consumer. This study showed that the addition of 2% and 4% palm oil in the feed of dairy sheep promoted a decrease in several SFAs associated with coronoary heart disease after 60 days of treatment. On the other hand, the addition of 6% palm oil promoted an increase of total SFA levels after 60 days of treatment, while decreaseing total PUFA levels. This can be considered harmful to consumers, since several SFA are associated with coronary heart diseases, and several PUFA are linked with reductions in inflammation, stroke, oxidative stress and hepatic disorders. In summary, the consumption of sheep milk who received the diets with 2% and 4% of palm oil can exert beneficial effects for consumers, and may be an option for farmers to increase the milk yield of sheep, and to reduce the profile of saturated fatty acids in milk.


2016 ◽  
Vol 43 (2) ◽  
pp. 207 ◽  
Author(s):  
Siria H. A. Natera ◽  
Camilla B. Hill ◽  
Thusitha W. T. Rupasinghe ◽  
Ute Roessner

Changes in lipid metabolism and composition as well as in distinct lipid species have been linked with altered plant growth, development and responses to environmental stresses including salinity. However, there is little information available in the literature focusing on lipids in roots under soil-related stresses such as salinity. Barley (Hordeum vulgare L.) is a major cereal grain and, as a glycophyte, suffers substantial yield loss when grown under saline conditions. Relatively little is understood of adaptation and tolerance mechanisms involving lipids and lipid metabolism in barley roots during development and under exposure to salinity stress. In this study we investigated the lipid composition of barley roots of Clipper and Sahara – two genotypes with contrasting responses to salinity – before and after salinity stress using a combination of three lipidomics techniques: Fatty acid compositional analysis, untargeted lipid profiling, and targeted analysis to profile quantitatively the individual molecular species of key plant lipid classes. Our results provide new insight into the effect of salinity on fatty acid profiles and key lipid classes within barley roots of two different genotypes, which is discussed in the context of current knowledge of the root metabolic responses of cereal crops to salinity stress.


2021 ◽  
Author(s):  
Manuel Flores Leon ◽  
Nicolas Alcaraz Millman ◽  
Martha Perez Dominguez ◽  
Karla Marisa Torres Arciga ◽  
Rosa Rebollar Vega ◽  
...  

Abstract The effects of the consumption of high-fat diets (HFD) have been studied to unravel the molecular pathways they are altering in order to understand the link between increased caloric intake, metabolic diseases, and the risk of cognitive dysfunction. The saturated fatty acid, palmitic acid (PA), is the main component of HFD and it has been found increased in the circulation of obese and diabetic people. In the central nervous system, PA has been associated with inflammatory responses in astrocytes, but the effects on neurons exposed to it have not been largely investigated. Given that PA affect a variety of metabolic pathways, we aimed to analyze the transcriptomic profile activated by this fatty acid to shed light on the mechanisms of neuronal dysfunction. In the current study, we profiled the transcriptome response after PA exposition at non-toxic doses in primary hippocampal neurons. Gene ontology and Reactome pathway analysis revealed a pattern of gene expression which is associated with inflammatory pathways, and importantly, with the activation of lipid metabolism that is considered not very active in neurons. Validation by qRT-PCR of Hmgcs2, Angptl4, Ugt8 and Rnf145 support the results obtained by RNAsEq. Overall, these findings suggest that neurons are able to respond to saturated fatty acids changing the expression pattern of genes associated with inflammatory response and lipid utilization that may be involved in the neuronal damage associated with metabolic diseases.


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