Biomedical subjects

S M Innis

Publications and source records attributed to S M Innis.

At least 91 records · Page 5Linked to original sources

PubMed1989

Changes in plasma cholesterol density distribution of young adult male rats fed a high fat and cholesterol diet following maternal cholestyramine treatment.

The effects of feeding cholestyramine to pregnant rats, which has been shown to increase the fetal hepatic rate-limiting enzyme in cholesterol synthesis, HMG CoA reductase, on the plasma cholesterol density distribution was studied in the young adult male rat offspring before and after feeding a diet high in fat and cholesterol. As in previous studies, offspring of rats fed cholestyramine during pregnancy had a plasma total cholesterol level similar to controls when fed a low fat and cholesterol diet, but higher than controls when fed a 20% (wt/wt) fat plus 5% (wt/wt) cholesterol diet. Analyses of the plasma cholesterol density distribution by continuous gradient ultracentrifugation showed that, compared to control rats, rats born to dams fed cholestyramine had more cholesterol in the higher density regions of plasma before and after a 7-d high fat and cholesterol diet challenge. After a 4- or 7-d diet challenge, rats fed cholestyramine had 2-3 times more cholesterol in the d less than or equal to 1.006 g/ml range of plasma compared to the control offspring. The results suggest that long term changes in cholesterol metabolism due to early nutrition in the rat may include altered plasma or intestinal lipoprotein metabolism, rather than an effect specific to hepatic cholesterol synthesis.

Animals↗

PubMed1989

Menhaden fish oil, n-3 polyunsaturated fatty acids, and protection of newborn rats from oxygen toxicity.

We have previously reported that newborn rats born to mothers fed a high n-6 polyunsaturated fatty acid (PUFA) (safflower oil) diet demonstrated increased n-6 PUFA in lung lipids and superior tolerance to high oxygen exposure. In the present study, we explored whether high n-3 PUFA might also protect against hyperoxic damage and by what mechanism. Adult female rats were fed either regular rat chow, a high n-3 (menhaden fish oil-based) diet, or a high n-6 (safflower oil-based) diet for 6 wk before and then throughout pregnancy and lactation. Newborn offspring of the high n-3 (fish oil) dams demonstrated increased n-3 PUFA (i.e. eicosapentaenoic and docosahexaenoic acid) and decreased n-6 PUFA (i.e. linoleic and arachidonic acid) in their lung lipids compared to the other two diet groups. The high n-6 (safflower oil) offspring had the opposite PUFA lung lipid pattern (with increases in total n-6 fatty acids and decreases in total n-3 fatty acids). The high n-3 offspring demonstrated markedly decreased lung levels of prostaglandin E2, F2 alpha and thromboxane B2, whereas the high n-6 offspring had higher eicosanoid levels than the regular diet offspring. Offspring of both high n-6 and high n-3 diet dams demonstrated essentially the same superior hyperoxic tolerance compared to regular diet offspring [7-d (greater than 95% O2) survival rates of 110/115 and 99/109, respectively, versus 70/91, p less than 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Effects of cortisol or corticotropin administration on hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity and plasma lipids in the pregnant rat and fetuses.

Pregnant rats were given pharmacological doses of cortisol or ACTH or no hormone from gestation day 9 to 19 and maternal and fetal hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity and plasma cholesterol studied on gestation day 20. Reductase activity was also studied in the maternal and fetal adrenal of the rats given cortisol or no hormone. Cortisol administration increased the maternal and fetal plasma cholesterol but had no effect on the hepatic active (phosphorylated) 3-hydroxy-3-methylglutaryl-CoA reductase activity when compared to untreated rats. Total (active + inactive) 3-hydroxy-3-methylglutaryl-CoA reductase activity, however, was reduced in maternal liver but not altered in the fetal liver by cortisol. The maternal cortisol treatment decreased the fetal, but not maternal, adrenal 3-hydroxy-3-methylglutaryl-CoA reductase total enzyme activity. The data support a hypothesis that utilization of plasma cholesterol for adrenal steroidogenesis may be an important determinant of plasma cholesterol homeostasis in the rat fetus. Maternal ACTH administration increased the foetal but not maternal plasma cholesterol, whilst active 3-hydroxy-3-methylglutaryl-CoA reductase activity was increased in the pregnant rat but not her fetuses. This result may suggest coordination of hepatic active reductase activity with adrenal cholesterol utilization in the pregnant rat. The reason for the fetal hypercholesterolaemia caused by ACTH, which is not known to cross the placenta, is uncertain. The studies, however, indicate that fetal cholesterol homeostasis and the rate limiting enzyme of cholesterol synthesis is influenced by maternal glucocorticoid administration.

Adrenocorticotropic Hormone↗

PubMed1989

Effects of cholestyramine feeding on tissue lipase activities and plasma fatty acids in the pregnant rat.

Rats fed a non-absorbable bile acid binding resin (cholestyramine) throughout gestation had decreased activities of adipose tissue lipoprotein lipase (LPL), hepatic triacylglycerol lipase and a heparin-releasable placental lipase distinct from LPL, when assayed at near-term gestation. The fetal plasma and liver triacylglycerol concentrations were not altered. The fetal liver total lipid and plasma triacylglycerol, however, had reduced levels of n-6 and n-3 series fatty acids, suggesting decreased availability of maternal dietary-derived essential fatty acids. These studies suggest that cholestyramine feeding may alter triacylglycerol flux and the quantity or type of maternal fatty acids available for placental transfer. The resin has application for in vivo study of the effects of maternal lipid transfer on the regulation of fetal hepatic lipid synthesis.

Animals↗

PubMed1989

Effect of linoleic acid-rich infant formula feeding on brain synaptosomal lipid accretion and enzyme thermotropic behavior in the piglet.

The effects of a vegetable oil-based infant formula, virtually devoid of n-6 and n-3 long chain polyenoid fatty acids (LCP) and high in 18:2(n-6) and 18:2(n-6)/18:3(n-3) ratio, on brain synaptosome lipid composition and enzyme thermotropic behavior were studied in neonatal piglets. Term gestation piglets were fed either sow milk (SMF) or formula (FF) from birth for 5, 10, 15, or 25 days. Synaptosomal cholesterol, total lipid phosphorus, and phospholipid class composition did not differ between SMF and FF piglets. Synaptosomal fatty acid composition, however, was influenced by diet. The proportion of n-3 LCP, especially 22:6(n-3), was decreased, while the n-6 LCP, especially 22:4(n-6) and 22:5(n-6), were increased in FF compared to SMF piglets. These diet-related changes were most pronounced in the ethanolamine glycerophospholipid fraction and increased with the duration of feeding. FF thus reversed an apparent developmental increase in the synaptosomal n-3/n-6 LCP ratio. The monoene content, especially 18:1, was also reduced in the synaptosomes of FF compared to SMF pigs. FF had no effect on the activity of synaptosomal acetylcholinesterase. However, higher transition temperatures for this enzyme, indicating decreased membrane fluidity, were found in the FF compared to SMF piglets. The data suggest that exclusive feeding of proprietary formulae, devoid of LCP and high in 18:2(n-6) and/or the 18:2 (n-6)/18:3(n-3) ratio, may compromise normal fatty acid accretion and physical properties of brain synaptosomal membranes.

Acetylcholinesterase↗

PubMed1988

Nonlinear estimation of parameters in biphasic Arrhenius plots.

This paper presents a formal procedure for the statistical analysis of data on the thermotropic behavior of membrane-bound enzymes generated using the Arrhenius equation and compares the analysis to several alternatives. Data is modeled by a bent hyperbola. Nonlinear regression is used to obtain estimates and standard errors of the intersection of line segments, defined as the transition temperature, and slopes, defined as energies of activation of the enzyme reaction. The methodology allows formal tests of the adequacy of a biphasic model rather than either a single straight line or a curvilinear model. Examples on data concerning the thermotropic behavior of pig brain synaptosomal acetylcholinesterase are given. The data support the biphasic temperature dependence of this enzyme. The methodology represents a formal procedure for statistical validation of any biphasic data and allows for calculation of all line parameters with estimates of precision.

Acetylcholinesterase↗

PubMed1988

Microsomal desaturation-elongation of linoleic acid following parenteral feeding with lipid emulsions in the rat.

The effect of total parenteral nutrition (TPN) with lipid emulsion to supply either 27.5% or 2% total calories on in vitro desaturation-elongation of 18:2(n-6) by liver microsomes was studied in the rat. The emulsion lipid contained ca. 50% 18:2(n-6) plus 8% 18:3(n-3) or 77% 18:2(n-6) plus 0.5% 18:3(n-3). The reaction rate was influenced by the in vitro substrate concentration and inhibited above 50 mumol 18:2(n-6)/mg microsomal protein. At maximum rates of desaturation-elongation, the formation of triene and tetraene (n-6) fatty acids was reduced in rats given either of the two emulsions. The rate of (n-6) pentaene formation was increased in rats given the emulsion with low 18:3(n-3) but not in rats given the emulsion with 8% 18:3(n-3). Analyses of the microsomal lipid indicated increased free cholesterol in all rats that received TPN. Esterified cholesterol was increased only in rats given 27.5% TPN calories as lipid. Microsomal total phospholipids and phospholipid class distributions were not altered by TPN. The data are consistent with reports of reduced levels of long-chain desaturation-elongation metabolites of 18:2(n-6) in tissue phospholipids following infusion of parenteral lipid. The data suggest that the mechanism may include alterations in other metabolic pathways such as cholesterol, in addition to desaturase enzyme activities, and may be influenced by both the quantity and fatty acid composition of the lipid infused.

Animals↗

PubMed1988

The composition of red cell membrane phospholipids in Canadian Inuit consuming a diet high in marine mammals.

A study of the fatty acid composition of red cell phosphatidylcholine and phosphatidylethanolamine and serum cholesterol was undertaken in 185 Canadian Inuit (age 2 months-82 years). Samples from 24 Canadian men and women (21-50 years) living in Vancouver were also analyzed as a reference for the Inuit in this age range. Dietary survey of the Inuit community (325 Inuit) demonstrated a diet based on traditional foods in which the principal source of n-3 fatty acid was marine mammal flesh (mean intake: 164 g/person/day) rather than fish (mean intake: 13 g/person/day). Compared to the Vancouver samples, the Inuit phosphatidylethanolamine had higher 20:5n-3 and 22:6n-3 and lower 20:4n-6, but similar 18:2n-6 levels. The level of 20:5n-3 was higher and 20:4n-6 was lower in the Inuit than in the Vancouver red cell phosphatidylcholine. Despite these differences in percentage content of C20 and C22 n-6 and n-3 fatty acids, the mean chain length and unsaturation index of the Inuit and Vancouver red cell phosphatidylcholine and phosphatidylethanolamine were very similar. Serum cholesterol concentration showed no sex difference within the Inuit, and no difference from Vancouver men and women of similar age. The analyses suggest that the fatty acid composition of the Inuit red cell phospholipids are primarily a reflection of their diet-fat composition.

Adolescent↗

PubMed1988

Long-chain n-3 fatty acids in breast milk of Inuit women consuming traditional foods.

The fatty acid composition of mature breast milk total lipids was analysed in milk from Inuit women living in a small Arctic community. Long-chain n-3 fatty acids were higher than in comparable samples from Vancouver residents. The data suggest that secretion of n-3 fatty acids in milk is influenced by the dietary intake of the lactating woman. The levels of these fatty acids in Inuit milk approximate those reported for the diet fat of adult Eskimo, and which have been associated with reduced plasma cholesterol levels and death from coronary heart disease.

British Columbia↗

PubMed1988

Polyunsaturated fatty acids and protection of newborn rats from oxygen toxicity.

To test whether polyunsaturated fatty acids (PUFA) might be associated with protection against oxygen toxicity in newborn experimental animals, we performed two series of experiments. In the first series, adult female rats were fed one of three diets--regular Rat Chow, a high-PUFA (safflower oil-based) diet, or a low-PUFA (palm oil-based) diet--for several weeks before and throughout pregnancy and lactation. Newborn offspring of the three diet groups had similar antioxidant enzyme activities and surfactant development. Offspring of dams fed the high-PUFA diet had total lung lipid fatty acids characterized by increased linoleic acid (18:2 omega 6) and arachidonic acid (20:4 omega 6) and a significantly increased PUFA/saturated fatty acid ratio, compared with offspring of dams fed the regular diet or low-PUFA diet; associated with this increased PUFA pattern was markedly superior survival (80 of 84 (95%) vs 56 of 84 (67%) for regular-diet offspring, P less than 0.01) after 7 days in greater than 95% oxygen. Conversely, offspring born to dams fed the low-PUFA diet had decreased lung PUFA content and inferior tolerance to prolonged high O2 exposure (survival 38 of 84 (45%)). In the second experimental series, the postnatal provision of high PUFA rat milk to offspring born to dams fed the low-PUFA diet (via "cross-nurturing" by high-PUFA diet dams) rapidly increased their lung lipid PUFA and improved their hyperoxic survival (44 of 50 vs 25 of 50 for low-PUFA diet newborn animals kept with their low-PUFA mother rats, P less than 0.01). These studies suggest that increasing lung lipid PUFA can confer a protective effect against the toxic effects of hyperoxia on the newborn animal lung.

Animals↗

PubMed1988

Effect of diet during pregnancy and lactation on the activity of HMG-CoA reductase in the developing rat.

Wistar rats were fed a control diet or a diet containing either cholestyramine or high fat and cholesterol throughout gestation and the first 14 d of lactation. New-born litters were cross-fostered from rats fed the control diet to rats fed either cholestyramine or high fat and cholesterol, or from rats fed cholestyramine to rats fed the control diet. Hepatic hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity, plasma cholesterol and triglycerides were assayed on gestation d 20 and postnatal d 8, 14, 22 and 30. Cholestyramine had no effect on maternal or fetal plasma lipid levels but increased fetal hepatic HMG-CoA reductase activity by approximately 50%. The increased reductase activity persisted on postnatal d 8 and 14. Control pups suckled by dams fed cholestyramine also had significantly increased HMG-CoA reductase activities on postnatal d 8 and 14. The high fat and cholesterol diet significantly increased maternal plasma cholesterol but had no effect on HMG-CoA reductase activity in the fetus or suckling pups. Neither cholestyramine nor high fat and cholesterol altered the rat milk cholesterol levels. The studies demonstrate that HMG-CoA reductase activity in the developing rat can be altered by factors dependent on maternal diet. They do not support a hypothesis for regulation by maternal dietary or milk cholesterol supply.

Animals↗

PubMed1988

Effect of chronic modification of diet fat and cholesterol during gestation on plasma hormones and hepatic enzyme activities in rat fetus.

Diet-induced elevation of cholesterol and corticosterone in pregnant rats had no effect on fetal plasma cholesterol or corticosterone, 3-hydroxy-3-methylglutaryl coenzyme A or hepatic reductase activities. The data suggest that increasing the maternal cholesterol pool has no effect on cholesterol transfer to, or metabolism in, the developing offspring, and that the late gestation fetus can maintain corticosterone levels appropriate to gestational age despite diet-induced elevations in the maternal plasma.

Acyl Coenzyme A↗

PubMed1988

Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in foetal rats by maternal cholestyramine feeding.

Late gestation foetus from rats fed a non-absorbable bile acid binding resin (cholestyramine) have increased hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. This was due to increased unphosphorylated (active) as well as total reductase and was accompanied by higher fatty acid synthetase activity. No increase in foetal hepatic cystathionase or tyrosine aminotransferase activity, or changes in plasma insulin, corticosterone or thyroxine were found. The studies demonstrate that foetal hepatic cholesterol metabolism is sensitive to drug-induced perturbation of maternal lipoprotein metabolism. The data suggest induction of foetal cholesterol and fatty acid synthesis by a specific mechanism not involving generalized hormone-induction of hepatic enzyme systems. Cholestyramine appears to have application for in vivo study of the regulation of foetal cholesterologenesis and its coordination to maternal and foetal steroid requirements.

Animals↗

PubMed1987

The fatty acid composition of Northern-Canadian marine and terrestrial mammals.

The low mortality from cardiovascular disease in Greenland Eskimos has been attributed to their consumption of diets rich in omega-3 fatty acids. These fatty acids are found in fish and marine mammal lipids. Whereas the fatty acid composition of several fish species has been documented, information is more limited on the mammals which feature significantly in the diets of many Arctic populations. This study investigated the fatty acid composition of commonly eaten marine mammals, as well as the polar bear and caribou. The tissue fatty acid composition was species-dependent, probably reflecting to some degree differences in feeding habits. The marine mammals and the amphibious polar bear, but not the caribou, contained substantial quantities of long chain omega-3 fatty acids. These studies further document the transfer of omega-3 fatty acids through the food chain to man and suggest that marine mammal and polar bear lipids are significant sources of omega-3 fatty acids.

Animals↗

PubMed1986

The activity of 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA: cholesterol acyltransferase in hepatic microsomes from male, female and pregnant rats. The effect of cholestyramine treatment and the relationship of enzyme activity to microsomal lipid composition.

The relationship of microsomal cholesterol and phospholipid fatty acid composition to the activities of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and acyl-CoA: cholesterol acyltransferase was investigated in male, female virgin and pregnant rats when hepatic cholesterogenesis was stimulated by cholestyramine. Cholestyramine increased HMG-CoA reductase activity in both sexes but had no effect on microsomal free cholesterol level or acyl-CoA: cholesterol acyltransferase activity. The data suggest that during cholestyramine treatment high rates of bile acid synthesis are supported by preferential channelling of cholesterol into this pathway, whilst the substrate pool and activity of acyl-CoA:cholesterol acyltransferase are maintained unaltered. The lack of a consistent relationship among enzyme activities and microsomal lipid composition infers that HMG-CoA reductase and acyl-CoA:cholesterol acyltransferase are regulated in vivo by independent mechanisms which are unlikely to involve modulation by the physical properties of the microsomal lipid.

Animals↗

PubMed1986

Effect of total parenteral nutrition with linoleic acid-rich emulsions on tissue omega 6 and omega 3 fatty acids in the rat.

The effect of total parenteral nutrition (TPN) with lipid emulsions containing ca. 48% 18:2 omega 6 plus 8% 18:3 omega 3 (Intralipid) or 76% 18:2 omega 6 plus 0.5% 18:3 omega 3 (Liposyn) on the fatty acid composition of liver and plasma triglyceride and phospholipid (PL) was studied in the rat. Plasma PL showed a clear influence of the egg PL present in the infused lipid, suggesting replacement of endogenous lipoprotein PL. The incorporation of 20 and 22 carbon omega 6 and omega 3 fatty acids was reduced in liver phosphatidylcholine of rats infused with either Intralipid or Liposyn. Phosphatidylethanolamine was much less affected and showed reduced 20:4 omega 6 and 20:5 omega 3 in the Liposyn group only. Reduction in levels of long chain essential fatty acid metabolites was compensated for by an increased content of saturated fatty acids. There was no accumulation of 18:2 omega 6 or 18:3 omega 3 in liver PL. The similarity between the effects of Intralipid and Liposyn supports the conclusion that 18:2 omega 6, not 18:3 omega 3, was responsible. The data suggest that intravenous administration of high levels of 18:2 omega 6 in parenteral lipid reduces desaturation/elongation of essential fatty acids but does not competitively inhibit esterification of other fatty acids into PL.

Animals↗

PubMed1985

The effect of total parenteral nutrition (TPN) on the enteroinsular axis in the rat.

The effect of 6 days of total parenteral nutrition (TPN) on the enteroinsular axis was studied in vivo and in vitro in the rat. During the TPN period, blood samples were taken from control and TPN animals to determine the comparative pattern of GIP release. Glucose, insulin and GIP responses to oral glucose (OGTT) were compared in TPN and control rats. The effect of glucose and GIP on insulin release from the isolated perfused pancreas of the same animals was investigated to determine if TPN altered the sensitivity of the beta cell. In conjunction with these studies the number and distribution of GIP-containing cells were compared in control and TPN animals. TPN resulted in no change in basal levels of glucose, insulin and IR-GIP. An exaggerated insulin response to OGTT occurred after TPN whereas the glucose response was reduced. The IR-GIP response to glucose was normal following TPN. The isolated perfused pancreas showed a 30% increase in insulin release in response to GIP after TPN. The insulin response to glucose appeared normal as did the number and distribution of GIP cells. Fluctuations in GIP and insulin levels in control animals were diurnal in nature, whereas IR-GIP levels in TPN animals remained near fasting levels. It was hypothesized that the increase in beta cell sensitivity to GIP may be causally connected to the exposure of the pancreas to chronically low levels of GIP during TPN.

Animals↗

PubMed1985

The effect of total parenteral nutrition in the rat on a sub-group of enteroendocrine cells.

The effect of total parenteral nutrition (TPN) in rats on a number of enteroendocrine cells was investigated. The rats were given a continuous intravenous infusion of basal TPN solution for 7 days. Samples from duodenum, jejunum and ileum were collected, immunostained and the immunoreactive cells quantified using a computerised morphometrics system. The endocrine cells containing somatostatin, cholecystokinin (CCK), gastric inhibitory polypeptide (GIP), neurotensin and enteroglucagon were investigated. The results demonstrated a significant reduction in the number of CCK cells in the duodenum and jejunum. In the ileum the neurotensin-immunoreactive cells were significantly increased in number (P less than 0.02). No change was seen in the number of cells immunostained for somatostatin, GIP or enteroglucagon. These data indicate that short term TPN has a definite effect on the enteroendocrine cell population which may be linked to the side effects of TPN seen in man.

Animals↗