A brief history of Progress in Lipid Research.
Explore the source record for details and available documents.
England↗
Biomedical subjects
R T Holman
Publications and source records attributed to R T Holman.
Effects of biotin deficiency on serum fatty acid composition: evidence for abnormalities in humans.
In three patients who developed biotin deficiency during parenteral alimentation, serum fatty acid compositions of the four major lipid classes (phospholipid, cholesteryl ester, triglyceride and free fatty acid) were measured. Relative to the normal range, percent compositions of an odd-chain fatty acid (either 15:0 or 17:0 or both) were increased in each class of lipid, and these abnormalities generally returned to normal or decreased toward normal with biotin therapy. Abnormalities in particular fatty acids in the omega 6, omega 3 and omega 9 pathways were also found, but these abnormalities did not resolve with biotin therapy. These data provide evidence in favor of the conclusion that biotin deficiency causes increases in the composition of some odd-chain fatty acids in humans, perhaps by the same mechanism that leads to odd-chain fatty acidemia in the inborn deficiency of the biotin-dependent enzyme propionyl-CoA carboxylase.
Acetyl-CoA Carboxylase↗
George O. Burr and the discovery of essential fatty acids.
Explore the source record for details and available documents.
Fatty Acids, Essential↗
Effects of biotin deficiency on plasma and tissue fatty acid composition: evidence for abnormalities in rats.
Abnormalities of fatty acid composition have been detected in the plasma of patients who developed frank biotin deficiency during parenteral nutrition. We sought to determine which abnormalities of fatty acid composition, if any, would be replicated in the biotin-deficient rat and to determine the relative temporal relationships of these abnormalities to biotin nutritional status. We measured fatty acid compositions of the phospholipids extracted from plasma, heart, and liver and assessed biotin nutritional status longitudinally in biotin-deficient and biotin-treated rats during progressive biotin deficiency. In the biotin-deficient group, significant increases relative to the biotin-treated group were detected in all three tissues in the odd-chain fatty acids 15:0 and 17:0. In the biotin-deficient rats, significant increases in 18:2 omega 6 in liver and 18:3 omega 6 in plasma and liver and significant decreases in 22:5 omega 6 were detected in plasma and liver. The constellation of fatty acid abnormalities observed in the biotin-deficient rats was not identical to that observed in biotin-deficient patients, but abnormalities in composition of odd-chain fatty acids were detected in both human and rat and therefore are attributable to biotin deficiency per se. The abnormalities in fatty acid composition were already present by wk 4 on the egg white diet; the cutaneous findings appeared between wk 3 and 6. These observations are consistent with the hypothesis that an abnormality in fatty acid metabolism may play a pathogenetic role in the cutaneous manifestations of biotin deficiency.
Animals↗
Fatty acid intake and Kupffer cell function: fish oil alters eicosanoid and monokine production to endotoxin stimulation.
Diets high in n-3 fatty acids appear to have an anti-inflammatory effect, which is thought to be due to decreased macrophage prostaglandin (PG) and thromboxane (Tx) production after incorporation of these fatty acids into cell membrane phospholipids. The effect of n-3 fatty acids incorporation on macrophage monokine release in response to septic stimuli is not well established. Kupffer cells, the fixed macrophages of the liver, were obtained from rats fed diets with fat sources derived from corn oil (CO, control), fish oil (FO, high in n-3 fatty acids), or safflower oil (SO, high in n-6 fatty acids) for 2 or 6 weeks. After exposure to bacterial lipopolysaccharide, Kupffer cells from rats fed FO for 2 or 6 weeks produced less PG and Tx than Kupffer cells from rats fed CO or SO. After 2 weeks of defined diets, interleukin-1 (IL-1) and tumor necrosis factor release were not affected by dietary fat source. In contrast, after 6 weeks of feeding, Kupffer cells from both the FO and the SO groups released less IL-1 and tumor necrosis factor when triggered by lipopolysaccharide than Kupffer's cells from animals fed the control diet that contained CO. These data suggest that altered monokine release from macrophages may contribute to the anti-inflammatory effect of diets high in n-3 fatty acids. Also shown in our results is that prolonged changes in membrane phospholipid content induced by dietary fat source can influence not only PG and Tx production but monokine release as well.
Animals↗
Mass spectra of the picolinyl esters of isomeric mono- and dienoic fatty acids.
The picolinyl ester derivatives of the complete series of isomeric octadecenoates, methylene-interrupted octadecadienoates, and of octadec-9-ynoate have been subjected to gas chromatography-mass spectrometry. A fused-silica capillary column, coated with a cross-linked methyl silicone, was used for the separation. Electron impact spectra were determined at 70 eV. Earlier observations with a limited series of model compounds were confirmed, and it was shown that the picolinyl ester derivatives were of almost universal value in the location of double bonds in such isomers. Difficulties of interpretation arose mainly when the double bonds were close to the carboxyl group.
Fatty Acids, Unsaturated↗
Efficacy of linoleic acid administered rectally as monoglyceride.
The potential of the rectal route for administration of essential fatty acids (EFA) as monoglyceride (MG) was investigated. EFA-deficient rats were supplemented with 14 mg linoleic acid/day for 3 days. Supplementation was either by oral administration as corn oil, orally as corn oil-derived MG or rectally as MG. The patterns of polyunsaturated fatty acids (PUFA) in liver and serum lipids, characteristic of EFA deficiency, were altered in the direction of normalcy in similar magnitude by all modes of supplementation, indicating that the rectal route may be useful for administration of EFA. The amounts of phospholipids (PL) and free fatty acids (FFA) in liver changed by all modes of administration. The magnitude of change of total PL and of FFA in liver depended upon the chemical form in which linoleic acid was administered and the route of administration, indicating that these factors affect lipid metabolism.
Animals↗
Essential fatty acid status in isolated closed head injury.
Abnormal profiles of polyunsaturated fatty acids in the plasma phospholipid fraction were observed in 14 patients with hypermetabolism due to severe isolated closed head injury. Depressed linoleic acid levels were observed within 24 hours along with elevation of oleic acid levels. By one week postinjury, subnormal levels of arachidonic acid were also observed. These data indicate that the metabolic response to injury encompasses changes in the metabolism of polyunsaturated fatty acids which are rapid in onset and qualitatively similar to those seen in mild essential fatty acid deficiency.
Adult↗
A comparison of pyrrolidide and picolinyl ester derivatives for the identification of fatty acids in natural samples by gas chromatography-mass spectrometry.
The pyrrolidide and picolinyl ester derivatives of the fatty acids in two natural lipid samples rich in unsaturated fatty acids, pig testis lipids and cod liver oil were satisfactorily resolved on capillary columns of fused silica coated with stationary phases of varying polarity. The picolinyl esters, in particular, when subjected to gas chromatography-mass spectrometry on a column containing a cross-linked methyl silicone, gave distinctive mass spectra, which could be interpreted in terms of both the numbers and positions of the double bonds.
Animals↗
Nutritional and biochemical evidences of acyl interaction with respect to essential polyunsaturated fatty acids.
Explore the source record for details and available documents.
Animals↗
Control of polyunsaturated acids in tissue lipids.
Since the discovery in 1929 that certain polyunsaturated fatty acids (PUFA) are essential for life and health, intense investigation has revealed the multiplicity of members in each of several families of PUFA, no two of which are equivalent. The quantified nutrient requirements for the essential dietary precursors of the two dominant families of PUFA have been estimated, and the general functions of these families are slowly becoming known. The PUFA are essential components of structural membrane lipids. The functions of the individual members are not yet differentiated, except as they act as precursors of synthesis of unique octadecanoid, eicosanoid, and docosanoid products of oxidation that have potent biological properties. The PUFA occur in animals and higher plants as ubiquitous and essential components of structural lipid that are in a dynamic equilibrium with the pool of dietary acyl groups. Many human diseases have been found to involve unique essential fatty acid (EFA) deficiencies or distortions of the normal equilibrium pattern. The equilibrium is influenced by the level of dietary intake or precursors, by the presence of competing essential and nonessential acyl groups, by nonoptimum intake of other essential nutrients, by hormonal effects, by drug therapy, and by other effects upon physiological condition. With the many variables already known to modulate or control the equilibrium, it should be possible with more precise understanding of each variable to shift abnormal equilibria in the direction of normalcy. This perhaps will be the next area of intensive investigation in this field of nutrition and metabolism.
Acrodermatitis↗
Nutritional and functional requirements for essential fatty acids.
Explore the source record for details and available documents.
Animals↗
Partial correction by exogenous lipid of abnormal patterns of polyunsaturated fatty acids in plasma phospholipids of stressed and septic surgical patients.
Polyunsaturated fatty acid (PUFA) profiles are abnormal in a variety of clinical conditions that are commonly seen in the surgical intensive care unit. PUFA profiles in the serum phospholipids were studied by capillary gas chromatography in 22 critically ill, hypermetabolic surgical intensive care unit patients. All patients received continuous total parenteral nutrition (TPN) by central vein with trace elements and vitamins. Eleven patients received daily supplementation with 50 gm of safflower oil-based lipid emulsion (TPN + L group). No lipid was administered in the other 11 patients (TPN). Both groups showed deficiencies in 18:2 omega 6 linoleic acid from the time of onset of TPN. In TPN the deficiency was progressive; in the TPN + L group, lipid administration prevented this progression but did not restore 18:2 omega 6 levels to normal. In the TPN group levels of 18:1 omega 9 and its metabolite 20:3 omega 9 (the triene of deficiency) increased over time, consistent with a mild essential fatty acid deficiency. These changes in omega 9 acids were not seen with lipid supplementation. Despite low levels of 18:2 omega 6 in both groups, the levels of omega 6 metabolites were normal or increased. Levels of 20:4 omega 6 (arachidonate) remained normal or slightly decreased in the TPN group but were decreased in the TPN + L group. Levels of arachidonate metabolites, in particular 22:5 omega 6, were increased in the lipid-supplemented group. We concluded that stressed patients receiving TPN develop mild essential fatty acid deficiency that is only partially correctable by lipid supplementation and that administration of supplemental lipid to these patients stimulates arachidonic acid conversion to 22:5 omega 6.
Aged↗
Essential fatty acid patterns in preeclampsia.
Fatty acid patterns were determined for maternal and cord sera from normal and preeclamptic pregnancies using gas liquid chromatography. Ten normal and 11 preeclamptic maternal sera were used; 6 preeclamptic and 6 normal cord sera were measured. Fatty acid patterns were measured in the nonesterified fatty acids (NEFA), the triglycerides (TG), the cholesterol esters (CE), and the phospholipids (PL). Preeclampsia showed significant differences in the essential fatty acid patterns in the maternal and cord sera compared to normal pregnancy. Oleic acid, an early indicator of essential fatty acid deficiency, made up a significantly greater proportion of preeclamptic cord blood NEFA, TG, and PL than in normal cord blood. Abnormalities in essential fatty acid patterns may be associated with decreased prostacyclin production and dysmaturity which may be seen with preeclampsia.
Arachidonic Acid↗
Synthesis of octadecynoic acids and [1-14C] labeled isomers of octadecenoic acids.
Geometric and positional isomers of [1-14C] octadecenoic acids have been synthesized by modifications of published procedures. Positional isomers of octadecynoic acids also have been synthesized to obtain the geometric and positional isomers of the unlabeled octadecenoic acid analogs. The syntheses were accomplished by coupling a haloalkyl compound with a substituted acetylene using n-butyl lithium in hexamethylphosphoramide. The coupled product, either a 17- or 18-carbon acetylenic alcohol, could be semihydrogenated and chain extended to afford a carboxy labeled derivative, could be partially hydrogenated and chain extended to afford a carboxyl labeled cis- or trans-octadecenoic acid in the former case. In the latter case, octadecynoic, cis-octadecenoic or trans-octadecenoic acids could be obtained by the appropriate reactions. The methods used in this study enabled the synthesis of 14C-labeled fatty acids in generally higher yields and by simpler reactions than were previously possible.
Isomerism↗
Dietary fats containing concentrates of cis or trans octadecenoates and the patterns of polyunsaturated fatty acids of liver phosphatidylcholine and phosphatidylethanolamine.
The effects of the mixed cis- 18:1 isomers and mixed trans- 18:1 isomers present in partially hydrogenated soybean oil (PHSO) upon the patterns of polyunsaturated fatty acids (PUFA) in liver phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were studied in rats fed concentrates of cis- 18:1 or trans- 18:1 isomers isolated as triacylglycerides from PHSO. The cis- 18:1 and trans- 18:1 concentrates were fed at levels equal to those present in PHSO fed at 17.9% of the diet. All diets contained the required amounts of both linoleic and linolenic acids. The trans- 18:1 concentrate was found to suppress the levels of 20:4 omega 6 and 20:3 omega 9, and to increase the levels of 18:2 omega 6 and 20:5 omega 3 in PC and PE. The cis- 18:1 concentrate suppressed 20:4 omega 6 in PC, 20:5 omega 3 in PC and PE, and 18:2 omega 6 in PC, but increased the levels of 20:4 omega 6 in PE, and 20:3 omega 9 in PC and PE. The cis- 18:1 concentrate was more effective than the trans concentrate in suppressing 22:6 omega 3. The trans- 18:1 concentrate was more effective in suppressing 20:4 omega 6. The trans- 18:1 isomers appear to modify PUFA metabolism by inhibition of PUFA synthesis, whereas the cis- 18:1 isomers appear to complete with 2-position fatty acyl transfer and to inhibit omega 3 PUFA acylation.
Animals↗
Effectiveness of dietary essential fatty acid deficiency in development of a model of endogenous renal prostaglandin deficiency.
An essential fatty acid deficient diet (EFAD) was administered to rats to determine the feasibility of using a model of endogenous arachidonic acid deficiency to study the role of prostaglandins in the kidney. Beginning at weaning rats were fed a diet containing less than 0.2% linoleic acid. Prostaglandin E (PGE) production was determined in vitro by stimulation of renal papillary slices with 1500 mOsm NaCl in Krebs-Henseleit buffer and in vivo by 24 hour urine collection. EFAD caused a reduction of arachidonic acid in the renal papilla to 13% of levels in control rats (P less than .0005). In vitro PGE release from incubated papillae of EFAD rats was barely detectable at baseline but increased with stimulation to approximately 50% of PGE levels observed in normal tissues. Urinary PGE, volume and sodium excretion were not significantly different between EFAD and control rats. These results suggest that despite significant differences in arachidonic acid stores between EFAD and normal rats, the usefulness of this animal model to study prostaglandin-mediated events may be limited by the residual capacity of the EFAD papilla to produce prostaglandin.
Animals↗
Biotin deficiency complicating parenteral alimentation: diagnosis, metabolic repercussions, and treatment.
Biotin deficiency associated with total parenteral nutrition is an emerging clinical problem; criteria for diagnosis and dosage for treatment are unclear. We have diagnosed and successfully treated biotin deficiency in three patients. Each patient had alopecia totalis, hypotonia, and developmental delay. Two developed the characteristic scaly periorificial dermatitis; one had only an intermittent scaly rash on the cheeks and occipital scalp. Zinc and essential fatty acid supplements were adequate; serum zinc levels and triene/tetraene ratios confirmed sufficiency of these nutrients. None of the patients received biotin prior to diagnosis, and each had decreased excretion of urinary biotin and increased urinary excretion of organic acids diagnostic of deficiency of two biotin-dependent enzymes (methylcrotonyl-coenzyme A carboxylase and priopionyl-coenzyme A carboxylase). Only one patient had a plasma biotin concentration below the normal range (Ochromonicas danica assay). The rash, alopecia, and neurologic findings responded dramatically to biotin therapy (100 micrograms/day in all patients; an initial larger dose of 1 mg/day for 1 week plus 10 mg/day for 7 weeks in one patient), and did not recur. However, abnormal organic acid excretion persisted in one patient who did not receive the larger dose. We conclude that plasma biotin concentration does not reflect biotin status in all cases and speculate that the biotin supplement currently recommended for pediatric patients (20 micrograms/day) may not be adequate therapy for biotin deficiency and might not even be adequate to maintain normal biotin status during TPN.
Alopecia↗