Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FATTY ACIDS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 793 records · Page 44Linked to original sources

Hormonal regulation of fatty acid synthetase, acetyl-CoA carboxylase and fatty acid synthesis in mammalian adipose tissue and liver.

The major objectives of this study were to define the roles of adrenal glucocorticoids and glucagon in the long-term regulation of fatty acid synthetase and acetyl-CoA carboxylase of mammalian adipose tissue and liver. Particular emphasis was given to elucidation of the mechanisms whereby these hormones produce their regulatory effects on enzymatic activity. To dissociate mental manipulation, nutritional conditions were ridgidly controlled in the experiments described. Administration of glucocorticoids to adult rats led to a marked reductionin activities of fatty acid synthetase and carboxylase in adipose in adipose tissue but no change occurred in liver. Adrenalectomy produced an increase in activities of these lipogenic enzymes in adipose tissure, but, again, no change was noted in liver. The decrease in enzymatic activities in adipose tissue with glucocorticoid administration correlated well with a decrease in fatty acid synthesis, determined in vivo by the 3-H2O method. The mechanisms whereby glucocorticoids led to a decrease in fatty acid synthetase activity were elucidated by the use of immunochemical techniques. Thus, the decrease in fatty acid synthetase activity observed in adipose tissue was shown to reflect a decrease in content of enzyme, and not a change in catalytic efficiency. The mechanism underlying the decrease in enzyme content is a decrease in synthesis of the enzyme. The relation of the effects of glucocorticoids to the effects of certain other hormones involved in regulation of lipogenesis was investigated in hypophysectomized and in diabetic animals. Thus, the observation that the glucocorticoid effect on synthetase and carboxylase occurred in adipose tissue of hypophysectomized rats indicated that alterations in levels of other pituitary-regulated hormones were not necessary for the effect. That glucocorticoids play some role in regulation of synthetase and carboxylase in liver, at lease in the diabetic state, was shown by the observation that the low activities of these enzymes in diabetic animals could be restored to normal by adrenalectomy. An even more pronounced restorative effect was apparent in adipose tissue of adrenalectomized, diabetic animals. Administration of glucagon during the refeeding of starved rats resulted in a marked reduction in the induction of fatty acid synthetase, acetyl-CoA carboxylase and in the rate of incorporation of 3-H from 3-H2O into fatty acids in liver, but no change in these parameters occurred in adipose tissue. Administration of theophylline resulted in intermediate reduction in liver. The mechanisms whereby glucagon led tto a decrease in fatty acid synthetase activity were elucidated by the use of immunochemical techniques. Thus, the changes in fatty acid synthetase activity were shown to reflect reductions in content of enzyme. The mechanism underlying these reductions in content is reduced synthesis of enzyme.

Acetyl-CoA Carboxylase↗

Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid oxidation in L6 myotubes.

We investigated the role of fatty acid availability on AMPK signalling and fatty acid oxidation in skeletal muscle. Incubating L6 skeletal muscle myotubes with palmitate (a saturated fatty acid) or linoleate (a polyunsaturated fatty acid) increased AMPK activity by 56 and 38%, respectively, compared with untreated cells. Consistent with these changes, AMPK Thr172 and acetyl-CoA carboxylase beta Ser218 phosphorylation were increased in fatty acid treated cells. Pre-incubating cells with palmitate or linoleate increased subsequent fatty acid oxidation by 86 and 92%, respectively. The enhanced AMPK signalling occurred in the absence of detectable changes in free AMP and glycogen content. The activity of the upstream kinase LKB1 was decreased by fatty acid treatment indicating that AMPK activation was not a consequence of LKB1 activation. Instead, fatty acids enhanced LKB1 phosphorylation of AMPK. Fatty acids did not alter LKB1 activity when either synthetic peptide or AMPK alpha(1-312) catalytic fragment was used as substrate indicating that the betagamma subunits were required for the fatty acid activation. Infection of cells with a dominant-negative AMPK adenovirus reduced basal fatty acid oxidation and inhibited the stimulatory effects of fatty acid pretreatment on fatty acid oxidation. These results indicate that increasing fatty acid availability increases AMPK activity independent of changes in the cellular energy charge and support the view that fatty acids may modulate AMPK allosterically, making it a better substrate for LKB1.

AMP-Activated Protein Kinase Kinases↗

Utilization of uniformly labeled 13C-polyunsaturated fatty acids in the synthesis of long-chain fatty acids and cholesterol accumulating in the neonatal rat brain.

Polyunsaturated fatty acids are needed for normal neonatal brain development, but the degree of conversion of the 18-carbon polyunsaturated fatty acid precursors consumed in the diet to their respective 20- and 22-carbon polyunsaturates accumulating in the brain is not well known. In the present study, in vivo 13C nuclear magnetic resonance spectroscopy was used to monitor noninvasively the brain uptake and metabolism of a mixture of uniformly 13C-enriched 16- and 18-carbon polyunsaturated fatty acid methyl esters injected intragastrically into neonatal rats. In vivo NMR spectra of the rat brain at postnatal days 10 and 17 had larger fatty acid signals than in uninjected controls, but changes in levels of individual fatty acids could not be distinguished. One day after injection of the U-13C-polyunsaturated fatty acid mixture, 13C enrichment (measured by isotope ratio mass spectrometry) was similar in brain phospholipids, free fatty acids, free cholesterol, and brain aqueous extract; 13C enrichment remained high in the phospholipids and cholesterol for 15 days. 13C enrichment was similar in the main fatty acids of the brain within 1 day of injection but 15 days later had declined in all except arachidonic acid while continuing to increase in docosahexaenoic acid. These changes in 13C enrichment in brain fatty acids paralleled the developmental changes in brain fatty acid composition. We conclude that, in the neonatal rat brain, dietary 16- and 18-carbon polyunsaturates are not only elongated and desaturated but are also utilized for de novo synthesis of long-chain saturated and monounsaturated fatty acids and cholesterol.

Aging↗

Digestion and absorption of polyunsaturated fatty acids.

Polyunsaturated fatty acids play an important part in the structure and function of cellular membranes and are precursors of lipid mediators which play a key role in cardiovascular and inflammatory diseases. Dietary sources of essential fatty acids are vegetable oils for either linoleic or alpha-linolenic acids, and sea fish oils for eicosapentaenoic and docosahexaenoic acids. Because of the specificity of the pancreatic lipid hydrolases, triglyceride fatty acid distribution is an essential parameter in the digestibility of fats. The efficiency of the intestinal uptake depends on the hydrolysis and especially on their micellarization. n-3 polyunsaturated fatty acid ethyl ester digestion is recognized to be impaired, but n-3 polyunsaturated fatty acid triglyceride hydrolysis remains a controversial point, and to some authors explains differences observed between vegetable and fish oil absorption. So additional studies are required to investigate this intestinal step. In enterocytes, morphological and biochemical absorption processes involve reesterification of long-chain fatty acids and lipoprotein formation. At this level, specific affinity of I- and L-FABPc (cytosolic fatty acid binding proteins) to polyunsaturated fatty acids requires further investigation. A better understanding of the role of these FABPc might bring to light the esterification step, particularly the integration of polyunsaturated fatty acids into phospholipids. With reference to differences published between fish and vegetable oil absorption, longer-term absorption studies appear essential to some authors. Polyunsaturated fatty acid absorption is thought to be not very dissimilar to that of long-chain mono-unsaturated fatty acid absorption. However, several digestion and absorption specific steps are worth studying with reference to the crucial role of polyunsaturated fatty acids in the organism, and for example adaptation of possible dietary supplements.

Dietary Fats, Unsaturated↗

Dietary clofibric acid increases intestinal fatty acid binding protein activity and apparent lipid digestibility in weanling swine.

The effects of supplementation of dietary clofibric acid (.5% wt/wt) on fatty acid binding protein (FABP) activity, apparent lipid digestibility, and serum cholesterol concentrations were evaluated in weanling pigs. Twenty-four barrows were allotted by weight and litter to a randomized complete block design with two treatments (basal vs clofibric acid) in six replicates. Nutrient digestibility measurements were made for a 2-wk period, after which the pigs were killed and tissues were collected. No differences in BW, liver, proximal small intestine, distal small intestine, and proximal and distal intestinal mucosa weights were observed. Apparent lipid digestibility was greater (P < .05) for the overall 2-wk period in clofibric acid-supplemented pigs (81.5 vs 76.6%). This paralleled the increased FABP activity in the distal small intestine (P < .001) of clofibric acid-supplemented pigs. Proximal intestine and liver FABP activities were unaffected by dietary treatment. Serum cholesterol concentrations were markedly lowered by clofibric acid supplementation. During wk 1, pigs fed the basal diet had twofold greater (P < .01) serum cholesterol concentrations, whereas during wk 2, basal-fed pigs had fourfold greater (P < .01) serum cholesterol concentrations (81.5 vs 18.3 mg/dL). These results suggest that elevated intestinal FABP activities may augment fatty acid absorption from the gastrointestinal tract.

Animal Feed↗

Reversible phenotypic modulation induced by deprivation of exogenous essential fatty acids.

Essential fatty acid deficiency, produced by deprivation of omega-6 and omega-3 fatty acids, is a condition characterized by renal disease, dermatitis, and infertility. Although many of the biochemical aspects of this disorder have been investigated, little is known about the ultrastructural changes induced by essential fatty acid deficiency. Using a unique fatty acid-deficient cell line (EFD-1), which demonstrates the in vivo fatty acid changes of essential fatty acid deficiency, and the prostaglandin E2-producing mouse fibrosarcoma line from which it was derived (HSDM1C1), we correlated ultrastructural and biochemical changes induced by prolonged deprivation of all exogenous lipids and subsequent repletion of selected essential fatty acids. We found that in cells deprived of all exogenous lipids, there was dilation of rough endoplasmic reticulum and an associated defect in protein secretion; these changes were specifically reversed by arachidonate. There was also an accumulation of secondary lysosomes containing degraded membranes in these cells with an associated increase in phospholipids relative to parent HSDM1C1 cells. Cytoplasmic lipid bodies present in parent cells disappeared, with an associated decrease in triacylglycerol. After just 2 days in lipid-free medium, all these changes were apparent, and prostaglandin E2 production was markedly impaired despite normal amounts of cellular arachidonate. Incubation of EFD-1 cells with arachidonate, the major prostaglandin precursor fatty acid, induced a reversion to the HSDM1C1 phenotype, whereas other fatty acids were totally ineffective. These results indicate changes in fatty acid metabolism in essential fatty acid deficiency are associated with marked alterations in ultrastructure and secretion of protein from cells.

Animals↗

Nutritional intervention high in vitamins, protein, amino acids, and omega3 fatty acids improves protein metabolism during the hypermetabolic state after thermal injury.

HYPOTHESIS: Characteristic of the hypermetabolic response to a thermal injury is the massive protein catabolism and compromised structure and function of essential organs. Nutrition has been suggested to affect protein metabolism and clinical outcome after a severe injury but published studies show controversial data. The purpose of this study was to determine the effect of enriched nutritional support during the postburn hypermetabolic state on protein metabolism in serum, liver, muscle, and skin. SETTING: Laboratory. INTERVENTION: Twenty-two rats were given burns covering 60% of their total body surface area and randomized to receive either standard rat chow (control) or a diet high in vitamins, protein, amino acids, and omega3 fatty acids. MAIN OUTCOME MEASURES: Five weeks after injury, body weight, serum, muscle, and hepatic protein content, insulin-like growth factor I concentration, and wound healing (reepithelization) were determined. RESULTS: Rats receiving the enriched diet showed a gradual improvement in body weight 1, 2, 3, 4, and 5 weeks postburn compared with controls (P< .001). Diet-fed rats demonstrated higher protein and insulin-like growth factor 1 content in serum, muscle, and liver 5 weeks after trauma (P< .001). Serum protein, albumin, and transferrin levels were significantly increased in rats receiving the diet compared with control rats (P< .001). Reepithelization was accelerated in rats receiving the enriched diet 4 (diet-fed, mean +/- SD, 23% +/- 1% vs controls, 17% +/- 1%; P< .001) and 5 (diet-fed, 24% +/- 1% vs controls, 18% +/- 1%; P< .001) weeks postburn compared with control rats. CONCLUSIONS: Nutritional intervention high in protein, vitamins, amino acids, and omega3 fatty acids improves protein net balance during the hypermetabolic response to thermal injury. Compromised organ function and structure and clinical outcome during the hypermetabolic response may be improved.

Animals↗

Synthesis of methyl-branched fatty acids from methylmalonyl-CoA by fatty acid synthase from both the liver and the harderian gland of the guinea pig.

Partially purified fatty acid synthase preparations from both the liver and the harderian gland of guinea pig showed the same relative rates of utilization of methylmalonyl-CoA when compared to malonyl-CoA. Radio gas-liquid chromatographic analysis of the products generated from [methyl-14C]methylmalonyl-CoA and from [2-14C]malonyl-CoA in the presence of unlabeled methylmalonyl-CoA showed that the enzyme from both tissues generated identical mixtures of branched fatty acids. Therefore, it is concluded that the production of methyl-branched acids only by the harderian gland is not due to any unique specificity of the fatty acid synthase of this gland, in contrast to the conclusion reached from results obtained from mass spectrometry of the products generated by crude extracts (Y. Seyama, H. Otsuka, A. Kawaguchi, and T. Yamakawa J. Biochem. 90, 789-797, 1981).

Acyl Coenzyme A↗

The conditional nature of the dietary need for polyunsaturates: a proposal to reclassify 'essential fatty acids' as 'conditionally-indispensable' or 'conditionally-dispensable' fatty acids.

The term essential fatty acid no longer clearly identifies the fatty acids it was originally used to describe. It would be more informative if the concept of essentiality shifted away from the symptoms arising from the lack of de novo synthesis of linoleate or alpha-linolenate and towards the adequacy of the capacity for synthesis and conservation of both the parent and the derived long-chain polyunsaturates. For instance, despite the existence of the pathway for synthesis of docosahexaenoate from alpha-linolenate, the former would be more correctly classified as 'conditionally indispensable' because the capacity of the pathway appears insufficient during early development, although it may be sufficient later in life in healthy individuals. Similarly, despite the inability to synthesize linoleate de novo, abundant linoleate stores and its relatively slow turnover in healthy adults probably makes linoleate 'conditionally dispensable' for long periods. There are two other anomalies with the terms essential and non-essential fatty acids: (1) under several different experimental circumstances, the C-skeleton of essential fatty acids is avidly used in the synthesis of non-essential fatty acids; (2) to function normally, the brain is required to endogenously synthesize several non-essential fatty acids. As with essential amino acids, which have been reclassified as indispensable or conditionally indispensable, such a change in terminology should lead to an improved understanding of the function and metabolism of polyunsaturates in particular, and long-chain fatty acids in general.

Fatty Acids, Essential↗

Acute regulation of fatty acid uptake involves the cellular redistribution of fatty acid translocase.

We used muscle contraction, which increases fatty acid oxidation, as a model to determine whether fatty acid transport is acutely regulated by fatty acid translocase (FAT/CD36). Palmitate uptake by giant vesicles, obtained from skeletal muscle, was increased by muscle contraction. Kinetic studies indicated that muscle contraction increased V(max), but K(m) remained unaltered. Sulfo-N-succinimidyl oleate, a specific inhibitor of FAT/CD36, fully blocked the contraction-induced increase in palmitate uptake. In giant vesicles from contracting muscles, plasma membrane FAT/CD36 was also increased in parallel with the increase in long chain fatty acid uptake. Further studies showed that like GLUT-4, FAT/CD36 is located in both the plasma membrane and intracellularly (endosomally). With muscle contraction, FAT/CD36 at the surface of the muscle was increased, while concomitantly, FAT/CD36 in the intracellular pool was reduced. Similar responses were observed for GLUT-4. We conclude that fatty acid uptake is subject to short term regulation by muscle contraction and involves the translocation of FAT/CD36 from intracellular stores to the sarcolemma, analogous to the regulation of glucose uptake by GLUT-4.

Animals↗

Lipid-lowering diets enriched with monounsaturated or polyunsaturated fatty acids but low in saturated fatty acids have similar effects on serum lipid concentrations in hyperlipidemic patients.

The aim of this study was to compare the effects of a diet enriched with monounsaturated (MUFAs) with one enriched with polyunsaturated (PUFAs) fatty acids on the serum lipoprotein composition in patients with hyperlipidemia. A new model for conducting controlled dietary treatment studies in free-living hyperlipidemic patients was tested. Twenty-six patients with an average age of 51 y participated in a crossover study during two consecutive 3.5-wk treatment periods. The mean serum cholesterol and LDL cholesterol decreased by 17% and 19%, respectively, on the MUFA diet. The corresponding figures on the PUFA diet were 19% and 23%, respectively. The HDL-cholesterol concentration was significantly decreased after both dietary periods. No significant differences in any of the variables studied were found between the diets. It is concluded that MUFAs and PUFAs, within a diet with a restricted content of saturated fat and total fat, are interchangeable with regard to lipid-lowering effects among free-living hyperlipidemic patients.

Adult↗

Fatty acid composition of Danish margarines and shortenings, with special emphasis on trans fatty acids.

Trans fatty acids from hydrogenated vegetable and marine oils could be as hypercholesterolemic and atherogenic as saturated fatty acids. Hence, it is important to know the fatty acid composition in major food contributors, e.g., margarines and shortenings. In 1992 margarines were examined, and in 1995 brands covering the entire Danish market were examined. Significant amounts of trans-18:1 were found only in hard margarines (mean: 4.2 +/- 2.8%) and shortenings (mean: 6.8 +/- 3.1%), whereas the semisoft and soft margarines contained substantially less trans-18:1 in 1995 than in 1992. Where marine oils had been used to a larger degree the mean trans-monoenoic content was about 15%, of which close to 50% was made up of long-chain (C20 and C22) trans fatty acids. A noteworthy decrease in the content of trans-18:1 had occurred for the semisoft margarines, from 9.8 +/- 6.1% in 1992 to 1.2 +/- 2.2% in 1995. Calculated from sales figures, the supply of trans-18:1 plus saturated fatty acids from margarines has decreased over this three-year period by 1.4 g/day, which has been replaced by cis monounsaturated and polyunsaturated fatty acids.

Chromatography, Gas↗

Control of fatty acid metabolism. I. Induction of the enzymes of fatty acid oxidation in Escherichia coli.

Escherichia coli grows on long-chain fatty acids after a distinct lag phase. Cells, preadapted to palmitate, grow immediately on fatty acids, indicating that fatty acid oxidation in this bacterium is an inducible system. This hypothesis is supported by the fact that cells grown on palmitate oxidize fatty acids at rates 7 times faster than cells grown on amino acids and 60 times faster than cells grown on a combined medium of glucose and amino acids. The inhibitory effect of glucose may be explained in terms of catabolite repression. The activities of the five key enzymes of beta-oxidation [palmityl-coenzyme A (CoA) synthetase, acyl-CoA dehydrogenase, enoyl-CoA hydrase, beta-hydroxyacyl-CoA dehydrogenase, and thiolase] all vary coordinately over a wide range of activity, indicating that they are all under unit control. The ability of a fatty acid to induce the enzymes of beta-oxidation and support-growth is a function of its chain length. Fatty acids of carbon chain lengths of C(14) and longer induce the enzymes of fatty acid oxidation and readily support growth, whereas decanoate and laurate do not induce the enzymes of fatty acid oxidation and only support limited growth of palmitate-induced cells. Two mutants, D-1 and D-3, which grow on decanoate and laurate were isolated and were found to contain constitutive levels of the beta-oxidation enzymes. Short-chain fatty acids (<C(8)) do not support growth of either the parent strain or the mutants D-1 and D-3. Evidence is also presented to show that decanoate is actively transported by the parent strain and by the mutants.

Acyltransferases↗