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Biomedical subjects

S C Mills

Publications and source records attributed to S C Mills.

At least 19 recordsLinked to original sources

The potential interactions between polyunsaturated fatty acids and colonic inflammatory processes.

n-3 Polyunsaturated fatty acids (PUFAs) are recognized as having an anti-inflammatory effect, which is initiated and propagated via a number of mechanisms involving the cells of the immune system. These include: eicosanoid profiles, membrane fluidity and lipid rafts, signal transduction, gene expression and antigen presentation. The wide-range of mechanisms of action of n-3 PUFAs offer a number of potential therapeutic tools with which to treat inflammatory diseases. In this review we discuss the molecular, animal model and clinical evidence for manipulation of the immune profile by n-3 PUFAs with respect to inflammatory bowel disease. In addition to providing a potential therapy for inflammatory bowel disease there is also recent evidence that abnormalities in fatty acid profiles, both in the plasma phospholipid membrane and in perinodal adipose tissue, may be a key component in the multi-factorial aetiology of inflammatory bowel disease. Such abnormalities are likely to be the result of a genetic susceptibility to the changing ratios of n-3 : n-6 fatty acids in the western diet. Evidence that the fatty acid components of perinodal adipose are fuelling the pro- or anti-inflammatory bias of the immune response is also reviewed.

Dietary Fats, Unsaturated↗

Effect of feeding protected lipids on fatty acid synthesis in ovine tissues.

The effects of including protected lipid supplements in the sheep diet have been studied by measuring the incorporation of [1-14C]acetate into tissue fatty acids in vivo and in vitro. Supplementing the diet with protected lipid significantly (P > 0.05) depressed lipogenesis in adipose tissue both in vovo and in vitro. However, when protected lipids of different fatty acid composition were given to lambs, the protected safflower oil supplement containing high levels of linoleic acid was the only treatment to cause a significant (P > 0.05) depression in fatty acid synthesis in adipose tissue, the major site of lipogenesis in the sheep. Larger adipose cells in the lipid-supplemented sheep indicate that these sheep were fatter than those receiving the basal diet. Therefore, supplemented wethers deposited more fat than sheep receiving the basal diet and this fat was derived from the supplement rather than from de novo synthesis.

Acetates↗

Ruminal hydrogenation of cholesterol.

Cholesterol was hydrogenated by anaerobic incubation with sheep rumen fluid for periods up to 20 hr. The principal product of cholesterol hydrogenation was identified as coprostanol. Cholesterol could be protected against in vitro ruminal hydrogenation by encapsulation in a matrix of formaldehyde-treated casein. Formaldehyde-treated casein-cholesterol preparations were also shown to be protected against hydrogenation in vivo and, when supplements containing 1 g per day of protected or unprotected cholesterol were fed to sheep over a period of 8-9 weeks, there were marked differences in the plasma cholesterol response. The plasma cholesterol of the sheep fed protected cholesterol increased by at least 60%. The plasma cholesterol of the sheep fed unprotected cholesterol also tended to increase during the first 5 weeks of supplementation but thereafter declined to almost control levels at 8 weeks.

Animals↗

The effect of dietary fat supplements on cholesterol metabolism in ruminants.

The serum cholesterol on ruminant animals rises when supplemental fat is fed in a form that ensures the absorption of long-chain fatty acids. The effects of these fat supplements on cholesterol metabolism have been studied in sheep and goats. The proximal part of the small intestine was the major site of sterol synthesis in sheep. Supplementing the diet with fat significantly enhanced sterolgenesis in the small intestine both in vivo and in vitro, whereas in vitro sterolgenesis appeared to be suppressed in the liver. Increased intestinal sterolgenesis was seen with several varieties of fat, but was greatest when palm oil was fed. The reciprocal findings in the intestine and liver may reflect the increased requirement for cholesterol for the transport of triglyceride in chylomicrons and the secondary inhibiting effect of this cholesterol on sterol synthesis in the liver. Dietary fat supplementation did not alter the excretion of neutral steroids in the feces of goats but did not cause a marked reduction in the excretion of acidic steroids which may have been due to the decreased formation of sterols in the liver. In two lactating goats in which an injection of [14C] cholesterol was followed by daily intraruminal administration of labeled cholesterol, fat supplementation lowered the specific radioactivity of cholesterol in alimentary particles and in milk, being consistent with an increase in intestinally synthesized cholesterol. The hypercholesterolemia that develops in fat-fed ruminants appears to be primarily due to an increased intestinal biosynthesis of cholesterol but may also be partly due to a decreased fecal excretion of bile acids.

Acetates↗

Effect of dietary fat supplementation on the composition and positional distribution of fatty acids in ruminant and porcine glycerides.

Dietary fats which were protected from ruminal metabolism were fed to ruminants, and the constituent fatty acids subsequently appeared in the glycerides of tissues and secretory products. These dietary fat induced alterations in tissue lipid composition were particularly apparent when the fat source was enriched with linoleic acid. Similarly, when pigs were fed linoleic-enriched fats, the linoleic acid was incorporated into the adipose tissue triglycerides. Stereospecific analyses were carried out on triglycerides from various tissues and secretory products obtained from animals fed control or linoleate-enriched diets. The analysis of adipose tissue triglycerides showed that linoleate and oleate were preferentially esterified to positions 2 and 3 (cattle and sheep), and positions 1 and 3 (pigs). Of the other major adipose tissue fatty acids, palmitate was preferentially esterified at position 1 (ruminants) and position 2 (pigs), and stearate was preferentially esterified at positions 1 and 3 (ruminants), and position 1 (pigs). Stereospecific analysis of high mol wt milk triglycerides showed that linoleate was either evenly distributed on all three positions (goats), or predominantly on position 3 (cows). Furthermore, the incorporation of this linoleate did not markedly alter the positional specificity of the other major milk triglyceride fatty acids. Of these fatty acids, the short and medium chain length acids (butyratelaurate) were mainly on position 3, myristate and palmitate on positions 1 and 2, and stearate and oleate evenly distributed. Thoracic duct lymph triglycerides from sheep tended to show preferential incorporation of linoleate at position 3, palmitate at position 2, and stearate at position 1 and 3; oleate, on the other hand, tended to be evenly distributed on all three positions of the lymph triglyceride. The stereospecific arrangement of fatty acids in sheep liver triglycerides was similar to that of lymph triglycerides, and this may reflect the uptake of intact or partially hydrolysed chylomicron and/or very low density lipoprotein triglycerides by the liver. There were also some analogies in the stereospecific arrangement of fatty acids on ruminant lymph and milk triglycerides and this may reflect an incomplete hydrolysis of chylomicron and/or very low density lipoprotein triglycerides prior to uptake by the mammary gland. An unusual feature of lymph from sheep fed linoleate was the presence of phospholipids which contained large amounts of linoleate in ca. equal proportion at both positions 1 and 2 of the phospholipid molecule.

Adipose Tissue↗

Effects of protected cyclopropene fatty acids on the composition of ruminant milk fat.

Unsaturated fatty acids can be protected from ruminal hydrogenation, and when fed to lactating ruminants, the constituent acids are incorporated into milk triacylglycerols. By this means, it has been possible to reduce the melting point of milk triglycerides and to make softer butter fat. This report shows that, by feeding small amounts of protected cyclopropene fatty acids, one is also able to make harder butter fat. Sterculia foetida seed oil, a rich source of cyclopropene fatty acids, was emulsified with casein and spray dried to yield a free flowing dry powder. When this material was treated with formaldehyde and fed to lactating goats(ca. 1 g cyclopropene fatty acids per day), there were substantial increases in the proportions of stearic acid and decreases in the proportions of oleic acid in milk fat. Similar results were obtained when the formaldehyde-treated supplements were fed to lactating cows (ca. 3 g cyclopropene fatty acids per day). The effect was considerably less apparent when the S. foetida seed oil-casein supplement was not treated with formaldehyde, suggesting that cyclopropene fatty acids are hydrogenated in the rumen as are other unsaturated fatty acids. The effect of feeding protected cyclopropene fatty acids on the stearic:oleic ratio in milk fat is probably due to cyclopropene-mediated inhibition of the mammary desaturase enzymes.

Animals↗

The mechanism of thyrotrophin action in relation to lipid metabolism in thyroid tissue.

1. The effects of thyrotrophin in vitro on the incorporation of [(14)C]-glucose, -glycerol, -palmitate and -oleate into the lipids of thyroid tissue were examined. 2. Thyrotrophin increased the incorporation of these (14)C-labelled precursors into phosphatidylinositol specifically. 3. Thyrotrophin also increased the proportion of (14)C radioactivity from labelled glucose, glycerol, palmitate and oleate incorporated into the 1,2-diglycerides. 4. The addition of thyrotrophin to thyroid slices for 10min., after 2hr. of prelabelling with [(14)C]glycerol, also increased the proportion of (14)C radioactivity incorporated into the 1,2-diglyceride fraction. 5. After incubation of thyroid tissue with [1-(14)C]palmitate, thyrotrophin caused a two- to three-fold increase in the specific radioactivity of palmitate isolated from phosphatidylinositol and 1,2-diglycerides. In contrast, the specific radioactivity of palmitate isolated from the choline and ethanolamine phosphoglycerides, 1,3-diglycerides and triglycerides was not increased by thyrotrophin.

Animals↗

Changes in plasma glucose, lactate and free fatty acids in lambs during summit metabolism and treatment with catecholamines.

1. Exposure to cold increased the plasma levels of glucose and lactate in young lambs (< 1-63 days old). Free fatty acid concentrations also increased, the increase being much greater in lambs older than 20 days.2. Intravenous infusions of adrenaline and noradrenaline into lambs under a neutral thermal environment caused large increases in plasma glucose, lactate and free fatty acids.3. Adrenaline and noradrenaline infusions increased the concentration of palmitic, stearic and oleic acids in the plasma of young lambs.4. Treatment of lambs in summit metabolism with either alpha- or beta-adrenergic blocking agents (phentolamine or propranolol, respectively) caused the plasma levels of free fatty acids to fall. Phentolamine hydrochloride decreased the concentration of plasma glucose, but did not change the lactate level. In contrast, propranolol decreased the concentration of both of these metabolites in a significant proportion of the experiments.5. Induction of muscular paralysis by suxamethonium chloride, in lambs exposed to cold, resulted in a rise in plasma free fatty acids, and a fall in glucose and lactate levels.6. These observations suggest that the circulating level of plasma metabolites in young lambs is not the limiting factor in the metabolic response to cold exposure.

Animals↗