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Biomedical subjects

S M Innis

Publications and source records attributed to S M Innis.

At least 109 records · Page 6Linked to original sources
PubMed1985

Hepatic transport of bile salt and bile composition following total parenteral nutrition with and without lipid emulsion in the rat.

The effect of total parenteral nutrition (TPN) on bile flow and composition and on hepatic bile acid transport maximum (Tm) and bile salt-independent bile flow (BSIF) was studied in the rat following seven days TPN containing 33% calories from Intralipid (IL) or Liposyn (LP) or 0% calories from lipid. All TPN regimes markedly reduced bile flow. In no case did TPN cause an increase in bile cholesterol concentration or saturation relative to bile acid and phospholipid. Bile acid Tm was reduced in rats receiving either 0% lipid or 33% IL; BSIF was reduced only in the 0% lipid group. Rats receiving 33% LP had a higher bile flow than the other TPN regimes while bile acid Tm and BSIF were similar to controls. It is proposed that in established TPN, bile flow is reduced largely as a result of decreased hepatic bile acid excretion. In the rat, TPN has no deleterious effect on the molar concentration of cholesterol, phospholipid or bile acid in bile secreted by the hepatocyte. The significant differences between the effect of the two lipid emulsions on hepatobiliary function require further study.

Animals↗
PubMed1985

The role of diet during development on the regulation of adult cholesterol homeostasis.

Atherosclerosis is believed to begin early in life and to develop over several decades. Elevated plasma cholesterol is a major contributing factor. Studies in animals have shown that manipulation of cholesterol metabolism during its development in pre- and early post-natal life can permanently alter cholesterol synthesis and catabolism to favour lower plasma cholesterol levels in the adult faced with a high dietary cholesterol intake. Although the mechanisms and pathways involved are likely to be different, "metabolic training" can occur as a result of both the diet fed to the mother during gestation and lactation and from the diet fed to the animal itself in early life. The presence of cholesterol itself in the suckling diet does not appear to confer any lasting improvement to cholesterol handling in either man or animals. Although much research is still required to define the time in development for effective training of specific steps in cholesterol metabolism and the primary site and mechanism of permanently altered metabolism, significant progress has been made. These studies will form the basis of this review.

Adult↗
PubMed1984

Altered effect of 3% dietary cholestyramine on plasma lipids and biliary bile acid output in the pregnant rat.

The effects of a diet containing 3% (w/w) cholestyramine on plasma total, free, and high-density lipoprotein cholesterol and triglycerides and on bile flow and composition were compared between pregnant rats fed the resin from before mating until the twentieth day of gestation and virgin rats fed the resin for an equivalent length of time. Pregnant and virgin rats consuming a similar diet but not receiving cholestyramine were also studied. In the nonpregnant rat the usual response to cholestyramine was observed as a significantly elevated plasma high-density lipoprotein cholesterol level and biliary bile acid secretion. Plasma cholesterol levels and bile composition were not altered by cholestyramine in the pregnant rat. The inability of resin therapy to change plasma high-density lipoprotein cholesterol and bile composition during pregnancy is likely to be causally related to a reduced efficacy of cholestyramine treatment when administered during gestation.

Animals↗
PubMed1984

Cholesterol oxidation and 7 alpha-hydroxylation during postnatal development of the rat.

The activity of rat hepatic cholesterol 7 alpha-hydroxylase is low in the suckling period and rises at weaning. The oxidation of intraperitoneally administered 26(-14)C-cholesterol to 14CO2 is also low in suckling rats and increases with age as does the radioactivity in the plasma. In contrast, propionic acid oxidation to CO2 is much more rapid, suggesting that the side chain cleavage of cholesterol is not a rate-limiting process.

Aging↗
PubMed1983

Effect of cholestyramine administration during pregnancy in the rat.

The effect of administration of cholestyramine on plasma cholesterol level and hepatic cholesterol and bile acid synthesis was investigated in pregnant and nonpregnant rats. Rates of cholesterol and bile acid synthesis were reduced by pregnancy in both control and cholestyramine-treated rats. Administration of cholestyramine throughout gestation and pregnancy failed either to lower plasma cholesterol level or to increase bile acid synthesis, while cholesterol synthesis was only moderately stimulated. It is suggested that pregnancy-induced alterations in hepatic bile flow and composition in the direction of cholestasis may be responsible for the decreased efficacy of cholestyramine given to the pregnant animal.

Animals↗
PubMed1983

Possible biotin deficiency in adults receiving long-term total parenteral nutrition.

Two adult patients receiving total parenteral nutrition on a long-term home basis presented with severe loss of hair. Both patients had extensive gut resection, consumed no biotin orally and received no biotin parenterally. Supplementation with Berroca-C, one ampule containing 200 micrograms biotin per day resulted in gradual regrowth of healthy hair. The patients now receive a parenteral solution containing biotin and have shown no recurrence of alopecia. It is suggested that biotin deficiency can occur in the adult when no preformed biotin is provided to the body and the contribution of this vitamin from intestinal microbial biosynthesis is compromised.

Adult↗
PubMed1983

Cholesterol and bile acid synthesis during total parenteral nutrition with and without lipid emulsion in the rat.

The origin of excess plasma free cholesterol known to accumulate in plasma of patients or animals given total parenteral nutrition (TPN) with lipid emulsion was investigated. Rats were infused for 8 days with a specially formulated TPN solution plus either lipid emulsion (lipid-TPN) or an equicaloric volume of 25% dextrose (dextrose-TPN). Laboratory diet-fed controls were sham operated. Lipid-TPN suppressed hepatic HMG CoA reductase (HMG CoAR) activity but elevated cholesterol 7 alpha-hydroxylase (7 alpha-OH) activity. HMG CoAR activity, however, was increased in adipose tissue and skeletal muscle by lipid-TPN when compared to dextrose-TPN. Plasma lecithin/cholesterol acyl transfer activity was similar among all groups. It is suggested that in lipid-TPN excess plasma free cholesterol does not arise from decreased hepatic clearance or plasma esterification but may originate from extrahepatic tissue, possibly through leaching of membrane cholesterol by mesophase phospholipid present in the lipid emulsion. The changes in hepatic HMG CoAR and 7 alpha-OH activity imply that during lipid-TPN plasma free cholesterol is cleared by the liver and catabolized to bile acid.

Acyl Coenzyme A↗
PubMed1983

Influence of maternal cholestyramine treatment on cholesterol and bile acid metabolism in adult offspring.

To reduce ileal reabsorption of bile acids and to deplete hepatic cholesterol pools, female rats were fed a diet containing 5% (wt/wt) cholestyramine from 4 days prior to mating. Control rats were fed the same diet without cholestyramine. In one group on day 20 of gestation diet-fed dams and their fetuses were investigated. Additional pups were raised in litters of eight and nursed by their mothers for 30 days at which time they were weaned to the control diet. All dams were given the control diet from day 14 of lactation; at no time did neonates have access to cholestyramine. Offspring were raised until 3 months of age then fed the control, cholestyramine or a high fat, high cholesterol diet for 5 days. Maternal cholestyramine produced significant elevation of fetal hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase; fetal 7 alpha-hydroxylase (7 alpha-OH) activity, plasma cholesterol and triglyceride levels, however, were not significantly altered. The elevated HMG-CoA reductase activity persisted in liver and in addition was present in jejunum of 3-month-old male offspring challenged with the control or cholestyramine diet for 5 days. When challenged with the high fat, high cholesterol diet, male offspring from cholestyramine-treated dams had significantly higher plasma cholesterol levels but HMG-CoA reductase and 7 alpha-OH activity similar to controls. Maternal treatment had no apparent effect on plasma triglyceride or hepatic 7 alpha-OH in 3-month-old male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Dynamic modulation of mitochondrial membrane physical properties and ATPase activity by diet lipid.

A longitudinal cross-over feeding design was used to investigate the relationship of dietary lipid composition to the membrane lipid environment and activity of mitochondrial ATPase in vivo. Rats were fed a polyunsaturated fatty-acid-rich oil (soya-bean oil) for 12 days, crossed-over to a monounsaturated fatty-acid-rich oil (rapeseed oil) for the next 11 days, then returned to soya-bean oil for 11 more days. Additional rats were fed either soya-bean oil or rapeseed oil throughout. Rats fed rapeseed oil had lower rates of ATPase-catalysed ATP/[32P]Pi exchange than rats fed soya-bean oil. Arrhenius plots showed higher transition temperature (Tt) and activation energy (Ea) for rats fed rapeseed oil. Switching from soya-bean oil to rapeseed oil was dynamically followed by changes in the thermotropic and kinetic properties of the mitochondrial ATPase exchange reaction. Returning to soya-bean oil reversed these changes. The rapid and reversible modulation of Tt caused by a change of the type of fat ingested suggests that membrane physicochemical properties are not under rigid intrinsic control but are continually modified by the profile of exogenously derived fatty acids. The studies suggest that in vivo the activity of mitochondrial ATPase is in part determined by dietary lipid via its influence on the microenvironment of the enzyme. The rapidity and ready reversibility of changes observed for this subcellular-membrane-bound enzyme suggest that dietary fatty-acid balance may be an important determinant of other membrane functions in the body.

Adenosine Triphosphatases↗
PubMed1981

Mitochondrial-membrane polar-head-group composition is influenced by diet fat.

Male Sprague-Dawley rats were fed diets containing 20% (w/w) soya-bean oil, high-erucic acid rapeseed oil or low-erucic acid rapeseed oil for 0, 12 or 23 days. The type of fat present in the diet had no effect on the total phospholipid content of heart mitochondria (micrograms/mg of protein) but did influence the phospholipid class distribution. Rats fed high-erucic acid rapeseed oil for 12 or 23 days had significantly higher mitochondrial phosphatidylcholine content than rats fed soya-bean oil. Low-erucic acid rapeseed oil resulted in elevation of cardiac mitochondrial cardiolipin content after dietary treatment for 12 days. The results demonstrate in vivo that diet is a significant determinant of the phospholipid class content of subcellular membranes.

Animals↗
PubMed1981

Dynamic modulation of mitochondrial inner-membrane lipids in rat heart by dietary fat.

A novel longitudinal feeding design was used to investigate the controlling influence of dietary fatty acids on the dynamic incorporation of fatty-acyl chains into phosphatidylcholine, phosphatidylethanolamine and cardiolipin in inner membrane of cardiac mitochondria. Rats were fed a polyunsaturated-fatty-acid-rich oil (soya-bean oil) for 12 days, crossed-over to a monounsaturated-fatty-acid-rich oil (rapeseed oil) for the next 11 days, then returned to soya-bean oil for 11 more days. Additional rats were fed either soya-bean oil or rapeseed oil only throughout. Rats were killed serially. Regression analysis was used to represent longitudinal flux in membrane lipid fatty-acid composition occurring with change in dietary fat. The fatty-acid composition of phosphatidylcholine, phosphatidylethanolamine and cardiolipin was influenced by dietary oil in a reversible way. Maximal diet influence was achieved in the 11-day cross-over period. Soya-bean oil to rapeseed oil cross-over caused the fatty-acid composition of phosphatidylcholine, phosphatidylethanolamine and cardiolipin to resemble that of rats fed rapeseed oil only. These changes were reversed by crossing back to soya-bean oil, indicating the dynamic state and short half-life of membrane phospholipid fatty-acyl chains. This report demonstrates for the first time in the whole animal fed diets adequate in all nutrients that subcellular membrane lipids rapidly respond to change in dietary fatty-acid balance. The system may be used to assess in vivo the significance of dietary fat in determining membrane physicochemical properties and biochemical functions.

Animals↗
PubMed1980

Effect of strain, sex and duration of feeding on plasma fatty acids of rats fed various dietary oils.

Experiments were conducted to determine if regression of cardiac lipidosis and strain or sex differences in susceptibility to cardiopathological change induced by rapeseed oils are coincident with physiological differences in fatty acid substrates supplied to the heart. Plasma fatty acid composition was determined in male Sprague-Dawley rats after 7 or 28 days and in female Sprague-Dawley and male Chester-Beatty rats after 28 days of feeding high or low erucic acid rapeseed oils, soybean oil or peanut oil. After 28 days, C14:0 and C18:1 fell and C20:4 increased as a percent of total fatty acid in all animals irrespective of oil fed, suggesting that changes in plasma fatty acids normally occur with development. Saturated and essential fatty acid profiles of male and female rats were different. Differences in plasma fatty acids stemming from sex-related physiological differences in whole body fat metabolism may form the basis of lower cardiopathological involvement for females. Results suggest physiological differences unrelated to plasma fatty acids determine strain differences in timing and severity of rapeseed oil-induced cardiac pathology.

Animals↗
PubMed1979

Effects of high and low erucic acid rapeseed oils on energy metabolism and mitochondrial function of the chick.

Duplicate experiments were conducted to compare energy utilization, growth, cardiac mitochondrial oxidative phosphoryl,tion, and mitochondrial membrane fatty acid composition of chicks fed diets containing 20 parts of high erucic acid rapeseed oil (HER), low erucic acid rapeseed oil (LER) or sunflower seed oil (SFO) for 24 days. Chicks fed diets containing HER deposited less fat and utilized energy less efficiently (kcal gained/kcal consumed) than chicks fed diets containing either LER or SFO. Energetic efficiency and fat deposition of chicks pair-fed diets containing LER were significantly lower than for chicks fed diets containing SFO. Cardiac mitochondria isolated from chicks fed diets containing either HER or LER for 24 days had significantly reduced ADP/O ratios and reduced rates of ATP synthesis utilizing pyruvate and malate as the respiratory substrates when compared with mitochondria isolated from chicks fed SFO. Diet induced transitions in fatty acid composition of cardiac mitochondrial membranes were also observed. The composition of fat ingested affected the fatty acid composition of mitochondrial diphosphatidyl glycerol more than the fatty acid composition of phosphatidyl choline or phosphatidyl ethanolamine. The linoleic acid content of mitochondrial diphosphatidyl glycerol was lower and the gadoleic acid and erucic acid content higher for chicks fed diets containing rapeseed oils than for chicks fed SFO containing diets. These studies indicate that a complex dynamic mechanism exists associating dietary fat with mitochondrial structural-functional changes and energetic efficiency in the growing chick.

Animals↗
PubMedDate not supplied

Does mitochondrial ATP synthesis decline as a function of change in the membrane environment with ageing.

Cardiac mitochondria isolated from rats fed purified diets of known lipid composition demonstrate a decline in the rates of oxidative phosphorylation, ATP synthesis and oligomycin sensitive ATPase activity as the animal ages. Transitions in these lipid-dependent functions of mitochondrial energy metabolism are concomitant with changes in the lipid environment of the mitochondrial membrane.

Adenosine Triphosphatases↗
PubMedDate not supplied

Effect of cholecystokinin-octapeptide on total parenteral nutrition-induced changes in hepatic bile secretion and composition in the rat.

These studies investigated the ability of twice-daily administration of cholecystokinin-octapeptide (CCK-8) to prevent changes in hepatic bile secretory function and bile composition resulting from total parenteral nutrition (TPN) in young, growing rats. Bile was collected from the common duct before and during i.v. infusion of sodium taurocholate following 7 days of TPN. TPN resulted in a reduction of hepatic bile flow, reduced bile molar cholesterol and phospholipid content, and reduction of the taurocholate secretory rate maximum (SRm) and bile salt-independent bile flow (BSIF). Rats treated with CCK-8 throughout their TPN retained high bile flows, BSIF, and SRm. CCK-8 at the dose used did not correct abnormalities in the hepatic bile composition or the magnitude of bile flow generated in response to i.v. taurocholate infusion. These findings suggest that the ability of CCK-8 to maintain high bile flows during TPN may have prophylactic relevance for prevention of TPN-induced gallbladder disease. However, these studies also suggest that a component of current TPN systems induces damage to hepatic bile metabolism and excretion that is additional to that due to the reduced stimulation of bile flow that accompanies elimination of oral food intake.

Animals↗
PubMedDate not supplied

The role of dietary n-6 and n-3 fatty acids in the developing brain.

The dietary requirements for essential fatty acids and the possibility of a specific role for the polyunsaturated fatty acid docosahexaenoic acid (DHA) is one of the most controversial areas in infant nutrition. DHA is found in unusually high concentrations in the brain and is selectively accumulated during fetal and infant brain growth. DHA can be synthesised through a complex series of chain elongation-desaturation reactions from alpha-linolenic acid, but the efficiency of this process in young infants is not clear. Clinical studies on the potential benefits to neural development of dietary DHA have yielded conflicting results. Recent studies have provided evidence that plasma DHA is available to developing brain and that DHA is involved in dopamine and serotonin metabolism. These findings should guide clinical studies to more sensitive measures of the functional roles of dietary n-3 fatty acids and to clinical conditions where n-3 fatty acids may have benefit.

Animals↗
PubMedDate not supplied

Serial measurement of plasma cholesterol and lecithin:cholesterol acyl transferase activity in adults receiving total parenteral nutrition.

The effect of total parenteral nutrition (TPN) containing approximately 800 ml Nutralipid daily on plasma cholesterol and lecithin:cholesterol acyl transferase (LCAT) activity was studied in 11 adult hospital patients. LCAT was assayed using an endogenous (S/N) and an artificial (ASA) substrate to differentiate between altered plasma substrate composition (which would influence the S/N method) and enzyme quantity (measured by the exogenous ASA method). Total cholesterol levels increased significantly during TPN, but generally remained within normal range. In comparison to laboratory reference values, free cholesterol was elevated and high-density lipoprotein cholesterol and ASA LCAT activity was reduced in patients before the start of TPN and remained unaltered by the TPN regime. S/N LCAT activity was normal and not altered by TPN. Since changes in plasma high-density lipoprotein and free cholesterol and ASA LCAT were present in patients before TPN, it must be concluded that they resulted from the underlying disease rather than the TPN per se. Longitudinal analyses showed that during the first 21 days of TPN nine patients showed a further fall in ASA LCAT and a rise in free cholesterol, thereafter ASA LCAT activity rose and free cholesterol fell despite continuation of TPN. It is suggested that ASA is a more reliable indicator of cholesterol esterification than S/N and that change in LCAT activity, although not caused by TPN, was related to the altered plasma lipid profile in the patients studied.

Adult↗