K. Botham - Academia.edu (original) (raw)

Papers by K. Botham

Research paper thumbnail of The influence of dietary saturated and unsaturated fat on hepatic cholesterol metabolism and the biliary excretion of chylomicron cholesterol in the rat

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1998

The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in ... more The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in long chain saturated fatty acids), olive oil (rich in monounsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids was studied in vivo in rats fed the corresponding oil in the diet for 21 days. The secretion of radioactivity into bile as both bile acids and unesterified cholesterol was significantly slower in the animals fed palm oil as compared to those given olive or corn oil, indicating that dietary saturated fat retards the excretion of cholesterol from the diet as compared to mono- or n-6 polyunsaturated fat. In order to investigate the mechanisms underlying these differences, the influence of the three high fat diets on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis in the liver and on biliary lipid output were also measured. The ratio of cholesterol esterification to cholesteryl ester hydrolysis was markedly raised in the olive and corn oil-fed as compared to palm oil-fed animals. Biliary cholesterol secretion was higher in corn oil-fed rats than in those fed olive or palm oil or a low fat diet, and this was associated with a markedly increased lithogenic index in these animals. The activity of cholesterol 7alpha hydroxylase was higher in the olive and corn oil-fed than in the palm oil-fed animals, although the expression of mRNA for the enzyme was increased only in the olive oil diet group. After 20 h biliary drainage, the rate of bile acid secretion into bile was increased in the rats fed olive and corn oil rather than to palm oil. These findings indicate that feeding rats mono- or n-6 polyunsaturated as compared to saturated fat in the diet promotes the storage of cholesteryl ester in the liver and leads to increased bile acid synthesis, resulting in the more rapid excretion of cholesterol originating from the diet via the bile.

Research paper thumbnail of Comprar Harper Bioquímica Ilustrada. Lange 30ª Ed. | Victor W. Rodwell | 9786071513687 | MCGRAW HILL

Tienda online donde Comprar Harper Bioquimica Ilustrada. Lange 30a Ed. al precio 105,05 € de Vict... more Tienda online donde Comprar Harper Bioquimica Ilustrada. Lange 30a Ed. al precio 105,05 € de Victor W. Rodwell | David A. Bender | K. Botham | P. Kennelly, tienda de Libros de Medicina, Libros de Biologia - Bioquimica

Research paper thumbnail of Harperova ilustrovaná biochemie

Research paper thumbnail of Comprar Harper's Illustrated Biochemistry 29th Ed. | A. Weil | 9780071765763 | Appleton & Lange

Tienda online donde Comprar Harper's Illustrated Biochemistry 29th Ed. al precio 51,17 € de A... more Tienda online donde Comprar Harper's Illustrated Biochemistry 29th Ed. al precio 51,17 € de A. Weil | V. Rodwell | P. Kennelly | K. Botham | D. Bender | R. Murray, tienda de Libros de Medicina, Libros de Biologia - Bioquimica

Research paper thumbnail of Comprar Harper. Bioquímica Ilustrada 29Ed Lange | K. Botham | 9786071509147 | MCGRAW HILL

Tienda online donde Comprar Harper. Bioquimica Ilustrada 29Ed Lange al precio 109,20 € de K. Both... more Tienda online donde Comprar Harper. Bioquimica Ilustrada 29Ed Lange al precio 109,20 € de K. Botham | D. Bender | David A. Bender | Robert K. Murray, tienda de Libros de Medicina, Libros de Quimica - Quimica

Research paper thumbnail of The utilisation of esterified and unesterifled cholesterol derived from chylomicron remnants and high density lipoprotein for bile acid synthesis

Biochemical Society Transactions, 1993

Research paper thumbnail of The effects of 6-azacholest-4-en-3β-ol-7-one, an inhibitor of cholesterol 7α-hydroxylase, on cholesterol metabolism and bile acid synthesis in primary cultures of rat hepatocytes

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1988

6-Azacholest-4-en-3/3-ol-7-one (azacholesterol) was shown to be a specific inhibitor of cholester... more 6-Azacholest-4-en-3/3-ol-7-one (azacholesterol) was shown to be a specific inhibitor of cholesterol 7a-hydroxylase. It inhibited cholesterol hydroxylation by a rat iiver microsomal preparation with non-competitive kinetics and a 1yi of 4 PM. No evidence was found for a time-blent inhibition of activity. Azachoiesterof did not inhibit acyl-CoA : cholesterol acyltransferase or 3-hy~xy-3-methylg~ut~~ coenzyme A reductase in rat liver microsomal preparations, or cholesterol esterification and synthesis in primary cultures of rat hepatocytes. The synthesis of bile acids was inhibited by azacholesterol in these cells in a dose-dependent way. When bile acid synthesis was inhibited by azacholesterol, newly-synthesised cholesterol from exogenous mevahmate was secreted by the hepatocyte cultures into the cell culture medium in severat-fofd excess over control incubations. No changes in the secretion of cholesteryi ester occurred in the presence of azacholesterol. This observation suggests that newly synthesised cholesterol that has entered the substrate pool for hydroxylation is no longer accessible to the substrate pool for esterification. This is further evidence for the compartmentation of cholesterol metabolism in the hepatocyte. introduction The liver presents one of the most complex patterns of intracellular cholesterol metabolism [I]. Because of its central role in cholesterol

Research paper thumbnail of Differential influence of different dietary fatty acids on very low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants

Metabolism, 2009

Differential influence of different dietary fatty acids on very lowdensity lipoprotein secretion ... more Differential influence of different dietary fatty acids on very lowdensity lipoprotein secretion when delivered to hepatocytes in chylomicron remnants

Research paper thumbnail of High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2  concentrations relative to a control high-oleic acid meal: a randomized controlled trial

American Journal of Clinical Nutrition, 2014

Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardio... more Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear. The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high-oleic acid meals; the secondary objective was to characterize the effects of linoleic acid-enriched high-fat meals relative to the control meal. We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high-oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high-linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35-70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L). Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0-3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse-reflection index was not significantly different. Plasma 8-isoprostane F2α analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed. These data show differential postprandial 8-isoprostane F2α responses to high-fat meals containing EPA + DHA-rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid-derived lipid mediators are required to determine possible divergent functional effects of single meals rich in either DHA or EPA. This trial was registered at clinicaltrials.gov as NCT01618071.

Research paper thumbnail of The contribution of lipoprotein cholesterol to hepatic precursor pools for bile acid synthesis

Biochemical Society transactions, 1992

... 1992 Nov;20(4):338S. The contribution of lipoprotein cholesterol to hepatic precursor pools f... more ... 1992 Nov;20(4):338S. The contribution of lipoprotein cholesterol to hepatic precursor pools for bile acid synthesis. Bravo E, Ortu G, Cantafora A, Guldur T, Mayes PA, Botham KM. Istituto Superiore di Sanita, Laboratory of Metabolism and Pathological Biochemistry, Rome, Italy. ...

Research paper thumbnail of Comparison of the hepatic metabolism of chylomicron remnants derived from corn oil or butter fat

Biochemical Society transactions, 1994

Research paper thumbnail of Comparison of the lipolysis of chylomicron remnants derived from corn oil or olive oil by hepatic lipase in vitro

Biochemical Society transactions, 1995

... Issue Date: 1995. Publisher: Biochemical Society. Citation: Botham KM, Mayes PA, Avella M, Ca... more ... Issue Date: 1995. Publisher: Biochemical Society. Citation: Botham KM, Mayes PA, Avella M, Cantafora A, Bravo E. Comparison of the lipolysis of chylomicron remnants derived from corn oil or olive oil by hepatic lipase in vitro. Biochemical society transactions 1995;23:284S. ...

Research paper thumbnail of The effect of portal blood bile salt concentrations on bile salt synthesis in rat liver

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1981

Research paper thumbnail of Portal blood concentraiions of conjugated cholic and chenodeoxycholic acids relationship to bile salt synthesis in liver cells

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1981

1. Rats were maintained in a strictly controlled environment of 12 h illumination and 12 h darkne... more 1. Rats were maintained in a strictly controlled environment of 12 h illumination and 12 h darkness. At regular intervals during the light/dark cycle the portal blood conjugated cholic acid and conjugated chenodeoxycholic acid concentrations were measured. The bile salt concentrations exhibited similar diurnal rhythms, the highest concentrations occurring in the middle of the dark phase. 2. The concentrations of conjugated cholic and chenodeoxycholic acids in the portal blood of rats fed a diet containing the bile salt sequestrant, cholestyramine, were significantly lower than those found in rats given a control diet. 3. During total biliary drainage the portal blood concentrations of conjugated cholic and chenodeoxycholic acids fell to a minimum 6-8 h after the start of the experiment, whereas bile salt synthesis in hepatocytes isolated from the rats was not increased until at least 13 h afer the commencement of total bilii drainage. 4. These results suggest that the concentrations of bile salts in the portal blood do not affect directly the diurnal fluctuation in rates of bile salt synthesis, as the response of synthesis to a change in portal blood bile salt concentrations is too slow. 5. When the rats were given a small supplement of cholesterol in the diet to suppress hepatic cholesterologenesis prior to being subjected to total biliary drainage, the changes in the portal blood concentrations of conjugated cholic and chenodeoxycholic acids and the synthesis of the two bile salts by isolated hepatocytes were similar to those found in rats given the control diet. 6. The rise in bile salt production seen during biliary drainage may not be dependent exclusively on a preceding increase in cholesterol synthesis.

Research paper thumbnail of The influence of dietary saturated and unsaturated fat on hepatic cholesterol metabolism and the biliary excretion of chylomicron cholesterol in the rat

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1998

The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in ... more The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in long chain saturated fatty acids), olive oil (rich in monounsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids was studied in vivo in rats fed the corresponding oil in the diet for 21 days. The secretion of radioactivity into bile as both bile acids and unesterified cholesterol was significantly slower in the animals fed palm oil as compared to those given olive or corn oil, indicating that dietary saturated fat retards the excretion of cholesterol from the diet as compared to mono- or n-6 polyunsaturated fat. In order to investigate the mechanisms underlying these differences, the influence of the three high fat diets on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis in the liver and on biliary lipid output were also measured. The ratio of cholesterol esterification to cholesteryl ester hydrolysis was markedly raised in the olive and corn oil-fed as compared to palm oil-fed animals. Biliary cholesterol secretion was higher in corn oil-fed rats than in those fed olive or palm oil or a low fat diet, and this was associated with a markedly increased lithogenic index in these animals. The activity of cholesterol 7alpha hydroxylase was higher in the olive and corn oil-fed than in the palm oil-fed animals, although the expression of mRNA for the enzyme was increased only in the olive oil diet group. After 20 h biliary drainage, the rate of bile acid secretion into bile was increased in the rats fed olive and corn oil rather than to palm oil. These findings indicate that feeding rats mono- or n-6 polyunsaturated as compared to saturated fat in the diet promotes the storage of cholesteryl ester in the liver and leads to increased bile acid synthesis, resulting in the more rapid excretion of cholesterol originating from the diet via the bile.

Research paper thumbnail of Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants

British Journal of Nutrition, 1996

Possible changes in the fatty acid composition of dietary fats and oils which might occur during ... more Possible changes in the fatty acid composition of dietary fats and oils which might occur during digestion, absorption and formation of chylomicrons and chylomicron remnants were investigated. Chylomicrons were collected from the thoracic duct of rats tube-fed with olive, maize, palm or fish oil or butter fat, and their fatty acid composition was determined and compared with that of their parent lipids. In turn, these lipoproteins were converted to chylomicron remnants in functionally hepatectomized rats and their composition re-determined. The predominant fatty acids in each of the oils and fats also predominated in their respective chylomicrons, but their proportions were reduced during the processes leading to their formation. Endogenous contributions of linoleic, eicosapentaenoic, and docosahexaenoic acids were particularly noted when these fatty acids were not well-represented in the original oils and fats, suggesting that they may be obligatory constituents in the formation of chylomicrons. The conversion of chylomicrons to remnants further attenuated the extremes in fatty acid composition of the dietary oils and fats. These results indicate that following an acute intake of oil or fat, the resulting chylomicrons and chylomicron remnants presented to the tissues contain a more balanced distribution of saturated, mono- and polyunsaturated fatty acids than the oils and fats from which they were derived.

Research paper thumbnail of The role of lipoprotein cholesterol in biliary steroid secretion. Studies with in vivo experimental models

Progress in Lipid Research, 1995

Research paper thumbnail of Differential effects of chylomicron remnants derived from corn oil or palm oil on bile acid synthesis and very low density lipoprotein secretion in cultured rat hepatocytes

Life Sciences, 1996

The effects of chylomicron remnants derived from corn oil (rich in n-6 polyunsaturated fatty acid... more The effects of chylomicron remnants derived from corn oil (rich in n-6 polyunsaturated fatty acids) and palm oil (rich in long chain saturated fatty acids) on bile acid synthesis and very low density lipoprotein secretion in cultured rat hepatocytes were studied. Incubation of the cells with corn oil remnants led to increased bile acid production, while the secretion of lipid in very low density lipoprotein remained unchanged. In contrast, addition of palm oil remnants to the medium did not affect bile acid synthesis, but resulted in the secretion of cholesterol-rich very low density lipoprotein. These findings show that chylomicron remnants of different fatty acid composition have differential effects on cholesterol metabolism in liver cells, and provide part of the explanation for the hyper- and hypocholesterolaemic effects of saturated and polyunsaturated fatty acids.

Research paper thumbnail of The effect of cyclic AMP analogues and glucagon on cholesteryl ester synthesis and hydrolysis in cultured hamster hepatocytes

FEBS Letters, 1993

Two cyclic AMP analogues, l-chloro cyclic AMP and 8-(4 chlorophenyltbio) cyclic AMP, were found t... more Two cyclic AMP analogues, l-chloro cyclic AMP and 8-(4 chlorophenyltbio) cyclic AMP, were found to increase the incorporation of rHJoleate into cholereryl ester in cultured hamster hapatocytes (30-40%), while incorporation into triacylglycerol was unaffected. An increase of a similar magnitude was observed in the presence of glucagon and the phosphodiesterase inhibitor, theophylline. The cyclic AMP analogues also stimulated the activity of neutral cholesteryl ester hydrolase in the cells, and this effect was mimicked by glucagon and theophylline. These results show that cyclic AMP can affect the cholesteryl ester cycle in hamster hepatocytes, and support the idea that the enzymes involved may be co-ordinately regulated.

Research paper thumbnail of A radioimmunoassay for tauro-β-muricholic acid suitable for use with isolated rat liver cells

FEBS Letters, 1983

A new radioimmunoassay which can be used to measure the amounts of tauro-&muricholic acid produce... more A new radioimmunoassay which can be used to measure the amounts of tauro-&muricholic acid produced by isolated rat hepatocytes in vitro is described. Cross reactivities of other bile acids known to be present in rat liver with the antiserum used in the assay were not sufficient to interfere with the measurement of tauro-fl-muricholic acid. Exogenous taurochenodeoxycholic acid was metabolised by isolated rat hepatocytes concurrently with the appearance of tauro-fl-muricholic acid in the cell.

Research paper thumbnail of The influence of dietary saturated and unsaturated fat on hepatic cholesterol metabolism and the biliary excretion of chylomicron cholesterol in the rat

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1998

The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in ... more The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in long chain saturated fatty acids), olive oil (rich in monounsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids was studied in vivo in rats fed the corresponding oil in the diet for 21 days. The secretion of radioactivity into bile as both bile acids and unesterified cholesterol was significantly slower in the animals fed palm oil as compared to those given olive or corn oil, indicating that dietary saturated fat retards the excretion of cholesterol from the diet as compared to mono- or n-6 polyunsaturated fat. In order to investigate the mechanisms underlying these differences, the influence of the three high fat diets on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis in the liver and on biliary lipid output were also measured. The ratio of cholesterol esterification to cholesteryl ester hydrolysis was markedly raised in the olive and corn oil-fed as compared to palm oil-fed animals. Biliary cholesterol secretion was higher in corn oil-fed rats than in those fed olive or palm oil or a low fat diet, and this was associated with a markedly increased lithogenic index in these animals. The activity of cholesterol 7alpha hydroxylase was higher in the olive and corn oil-fed than in the palm oil-fed animals, although the expression of mRNA for the enzyme was increased only in the olive oil diet group. After 20 h biliary drainage, the rate of bile acid secretion into bile was increased in the rats fed olive and corn oil rather than to palm oil. These findings indicate that feeding rats mono- or n-6 polyunsaturated as compared to saturated fat in the diet promotes the storage of cholesteryl ester in the liver and leads to increased bile acid synthesis, resulting in the more rapid excretion of cholesterol originating from the diet via the bile.

Research paper thumbnail of Comprar Harper Bioquímica Ilustrada. Lange 30ª Ed. | Victor W. Rodwell | 9786071513687 | MCGRAW HILL

Tienda online donde Comprar Harper Bioquimica Ilustrada. Lange 30a Ed. al precio 105,05 € de Vict... more Tienda online donde Comprar Harper Bioquimica Ilustrada. Lange 30a Ed. al precio 105,05 € de Victor W. Rodwell | David A. Bender | K. Botham | P. Kennelly, tienda de Libros de Medicina, Libros de Biologia - Bioquimica

Research paper thumbnail of Harperova ilustrovaná biochemie

Research paper thumbnail of Comprar Harper's Illustrated Biochemistry 29th Ed. | A. Weil | 9780071765763 | Appleton & Lange

Tienda online donde Comprar Harper's Illustrated Biochemistry 29th Ed. al precio 51,17 € de A... more Tienda online donde Comprar Harper's Illustrated Biochemistry 29th Ed. al precio 51,17 € de A. Weil | V. Rodwell | P. Kennelly | K. Botham | D. Bender | R. Murray, tienda de Libros de Medicina, Libros de Biologia - Bioquimica

Research paper thumbnail of Comprar Harper. Bioquímica Ilustrada 29Ed Lange | K. Botham | 9786071509147 | MCGRAW HILL

Tienda online donde Comprar Harper. Bioquimica Ilustrada 29Ed Lange al precio 109,20 € de K. Both... more Tienda online donde Comprar Harper. Bioquimica Ilustrada 29Ed Lange al precio 109,20 € de K. Botham | D. Bender | David A. Bender | Robert K. Murray, tienda de Libros de Medicina, Libros de Quimica - Quimica

Research paper thumbnail of The utilisation of esterified and unesterifled cholesterol derived from chylomicron remnants and high density lipoprotein for bile acid synthesis

Biochemical Society Transactions, 1993

Research paper thumbnail of The effects of 6-azacholest-4-en-3β-ol-7-one, an inhibitor of cholesterol 7α-hydroxylase, on cholesterol metabolism and bile acid synthesis in primary cultures of rat hepatocytes

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1988

6-Azacholest-4-en-3/3-ol-7-one (azacholesterol) was shown to be a specific inhibitor of cholester... more 6-Azacholest-4-en-3/3-ol-7-one (azacholesterol) was shown to be a specific inhibitor of cholesterol 7a-hydroxylase. It inhibited cholesterol hydroxylation by a rat iiver microsomal preparation with non-competitive kinetics and a 1yi of 4 PM. No evidence was found for a time-blent inhibition of activity. Azachoiesterof did not inhibit acyl-CoA : cholesterol acyltransferase or 3-hy~xy-3-methylg~ut~~ coenzyme A reductase in rat liver microsomal preparations, or cholesterol esterification and synthesis in primary cultures of rat hepatocytes. The synthesis of bile acids was inhibited by azacholesterol in these cells in a dose-dependent way. When bile acid synthesis was inhibited by azacholesterol, newly-synthesised cholesterol from exogenous mevahmate was secreted by the hepatocyte cultures into the cell culture medium in severat-fofd excess over control incubations. No changes in the secretion of cholesteryi ester occurred in the presence of azacholesterol. This observation suggests that newly synthesised cholesterol that has entered the substrate pool for hydroxylation is no longer accessible to the substrate pool for esterification. This is further evidence for the compartmentation of cholesterol metabolism in the hepatocyte. introduction The liver presents one of the most complex patterns of intracellular cholesterol metabolism [I]. Because of its central role in cholesterol

Research paper thumbnail of Differential influence of different dietary fatty acids on very low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants

Metabolism, 2009

Differential influence of different dietary fatty acids on very lowdensity lipoprotein secretion ... more Differential influence of different dietary fatty acids on very lowdensity lipoprotein secretion when delivered to hepatocytes in chylomicron remnants

Research paper thumbnail of High-fat meals rich in EPA plus DHA compared with DHA only have differential effects on postprandial lipemia and plasma 8-isoprostane F2  concentrations relative to a control high-oleic acid meal: a randomized controlled trial

American Journal of Clinical Nutrition, 2014

Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardio... more Eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation has beneficial cardiovascular effects, but postprandial influences of these individual fatty acids are unclear. The primary objective was to determine the vascular effects of EPA + DHA compared with DHA only during postprandial lipemia relative to control high-oleic acid meals; the secondary objective was to characterize the effects of linoleic acid-enriched high-fat meals relative to the control meal. We conducted a randomized, controlled, double-blind crossover trial of 4 high-fat (75-g) meals containing 1) high-oleic acid sunflower oil (HOS; control), 2) HOS + fish oil (FO; 5 g EPA and DHA), 3) HOS + algal oil (AO; 5 g DHA), and 4) high-linoleic acid sunflower oil (HLS) in 16 healthy men (aged 35-70 y) with higher than optimal fasting triacylglycerol concentrations (mean ± SD triacylglycerol, 1.9 ± 0.5 mmol/L). Elevations in triacylglycerol concentration relative to baseline were slightly reduced after FO and HLS compared with the HOS control (P < 0.05). The characteristic decrease from baseline in plasma nonesterified fatty acids after a mixed meal was inhibited after AO (Δ 0-3 h, P < 0.05). HLS increased the augmentation index compared with the other test meals (P < 0.05), although the digital volume pulse-reflection index was not significantly different. Plasma 8-isoprostane F2α analysis revealed opposing effects of FO (increased) and AO (reduced) compared with the control (P < 0.05). No differences in nitric oxide metabolites were observed. These data show differential postprandial 8-isoprostane F2α responses to high-fat meals containing EPA + DHA-rich fish oil compared with DHA-rich AO, but these differences were not associated with consistent effects on postprandial vascular function or lipemia. More detailed analyses of polyunsaturated fatty acid-derived lipid mediators are required to determine possible divergent functional effects of single meals rich in either DHA or EPA. This trial was registered at clinicaltrials.gov as NCT01618071.

Research paper thumbnail of The contribution of lipoprotein cholesterol to hepatic precursor pools for bile acid synthesis

Biochemical Society transactions, 1992

... 1992 Nov;20(4):338S. The contribution of lipoprotein cholesterol to hepatic precursor pools f... more ... 1992 Nov;20(4):338S. The contribution of lipoprotein cholesterol to hepatic precursor pools for bile acid synthesis. Bravo E, Ortu G, Cantafora A, Guldur T, Mayes PA, Botham KM. Istituto Superiore di Sanita, Laboratory of Metabolism and Pathological Biochemistry, Rome, Italy. ...

Research paper thumbnail of Comparison of the hepatic metabolism of chylomicron remnants derived from corn oil or butter fat

Biochemical Society transactions, 1994

Research paper thumbnail of Comparison of the lipolysis of chylomicron remnants derived from corn oil or olive oil by hepatic lipase in vitro

Biochemical Society transactions, 1995

... Issue Date: 1995. Publisher: Biochemical Society. Citation: Botham KM, Mayes PA, Avella M, Ca... more ... Issue Date: 1995. Publisher: Biochemical Society. Citation: Botham KM, Mayes PA, Avella M, Cantafora A, Bravo E. Comparison of the lipolysis of chylomicron remnants derived from corn oil or olive oil by hepatic lipase in vitro. Biochemical society transactions 1995;23:284S. ...

Research paper thumbnail of The effect of portal blood bile salt concentrations on bile salt synthesis in rat liver

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1981

Research paper thumbnail of Portal blood concentraiions of conjugated cholic and chenodeoxycholic acids relationship to bile salt synthesis in liver cells

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1981

1. Rats were maintained in a strictly controlled environment of 12 h illumination and 12 h darkne... more 1. Rats were maintained in a strictly controlled environment of 12 h illumination and 12 h darkness. At regular intervals during the light/dark cycle the portal blood conjugated cholic acid and conjugated chenodeoxycholic acid concentrations were measured. The bile salt concentrations exhibited similar diurnal rhythms, the highest concentrations occurring in the middle of the dark phase. 2. The concentrations of conjugated cholic and chenodeoxycholic acids in the portal blood of rats fed a diet containing the bile salt sequestrant, cholestyramine, were significantly lower than those found in rats given a control diet. 3. During total biliary drainage the portal blood concentrations of conjugated cholic and chenodeoxycholic acids fell to a minimum 6-8 h after the start of the experiment, whereas bile salt synthesis in hepatocytes isolated from the rats was not increased until at least 13 h afer the commencement of total bilii drainage. 4. These results suggest that the concentrations of bile salts in the portal blood do not affect directly the diurnal fluctuation in rates of bile salt synthesis, as the response of synthesis to a change in portal blood bile salt concentrations is too slow. 5. When the rats were given a small supplement of cholesterol in the diet to suppress hepatic cholesterologenesis prior to being subjected to total biliary drainage, the changes in the portal blood concentrations of conjugated cholic and chenodeoxycholic acids and the synthesis of the two bile salts by isolated hepatocytes were similar to those found in rats given the control diet. 6. The rise in bile salt production seen during biliary drainage may not be dependent exclusively on a preceding increase in cholesterol synthesis.

Research paper thumbnail of The influence of dietary saturated and unsaturated fat on hepatic cholesterol metabolism and the biliary excretion of chylomicron cholesterol in the rat

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1998

The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in ... more The biliary excretion of [3H] cholesterol carried in chylomicrons derived from palm oil (rich in long chain saturated fatty acids), olive oil (rich in monounsaturated fatty acids) or corn oil (rich in n-6 polyunsaturated fatty acids was studied in vivo in rats fed the corresponding oil in the diet for 21 days. The secretion of radioactivity into bile as both bile acids and unesterified cholesterol was significantly slower in the animals fed palm oil as compared to those given olive or corn oil, indicating that dietary saturated fat retards the excretion of cholesterol from the diet as compared to mono- or n-6 polyunsaturated fat. In order to investigate the mechanisms underlying these differences, the influence of the three high fat diets on cholesterol esterification, cholesteryl ester hydrolysis and bile acid synthesis in the liver and on biliary lipid output were also measured. The ratio of cholesterol esterification to cholesteryl ester hydrolysis was markedly raised in the olive and corn oil-fed as compared to palm oil-fed animals. Biliary cholesterol secretion was higher in corn oil-fed rats than in those fed olive or palm oil or a low fat diet, and this was associated with a markedly increased lithogenic index in these animals. The activity of cholesterol 7alpha hydroxylase was higher in the olive and corn oil-fed than in the palm oil-fed animals, although the expression of mRNA for the enzyme was increased only in the olive oil diet group. After 20 h biliary drainage, the rate of bile acid secretion into bile was increased in the rats fed olive and corn oil rather than to palm oil. These findings indicate that feeding rats mono- or n-6 polyunsaturated as compared to saturated fat in the diet promotes the storage of cholesteryl ester in the liver and leads to increased bile acid synthesis, resulting in the more rapid excretion of cholesterol originating from the diet via the bile.

Research paper thumbnail of Modification of the fatty acid composition of dietary oils and fats on incorporation into chylomicrons and chylomicron remnants

British Journal of Nutrition, 1996

Possible changes in the fatty acid composition of dietary fats and oils which might occur during ... more Possible changes in the fatty acid composition of dietary fats and oils which might occur during digestion, absorption and formation of chylomicrons and chylomicron remnants were investigated. Chylomicrons were collected from the thoracic duct of rats tube-fed with olive, maize, palm or fish oil or butter fat, and their fatty acid composition was determined and compared with that of their parent lipids. In turn, these lipoproteins were converted to chylomicron remnants in functionally hepatectomized rats and their composition re-determined. The predominant fatty acids in each of the oils and fats also predominated in their respective chylomicrons, but their proportions were reduced during the processes leading to their formation. Endogenous contributions of linoleic, eicosapentaenoic, and docosahexaenoic acids were particularly noted when these fatty acids were not well-represented in the original oils and fats, suggesting that they may be obligatory constituents in the formation of chylomicrons. The conversion of chylomicrons to remnants further attenuated the extremes in fatty acid composition of the dietary oils and fats. These results indicate that following an acute intake of oil or fat, the resulting chylomicrons and chylomicron remnants presented to the tissues contain a more balanced distribution of saturated, mono- and polyunsaturated fatty acids than the oils and fats from which they were derived.

Research paper thumbnail of The role of lipoprotein cholesterol in biliary steroid secretion. Studies with in vivo experimental models

Progress in Lipid Research, 1995

Research paper thumbnail of Differential effects of chylomicron remnants derived from corn oil or palm oil on bile acid synthesis and very low density lipoprotein secretion in cultured rat hepatocytes

Life Sciences, 1996

The effects of chylomicron remnants derived from corn oil (rich in n-6 polyunsaturated fatty acid... more The effects of chylomicron remnants derived from corn oil (rich in n-6 polyunsaturated fatty acids) and palm oil (rich in long chain saturated fatty acids) on bile acid synthesis and very low density lipoprotein secretion in cultured rat hepatocytes were studied. Incubation of the cells with corn oil remnants led to increased bile acid production, while the secretion of lipid in very low density lipoprotein remained unchanged. In contrast, addition of palm oil remnants to the medium did not affect bile acid synthesis, but resulted in the secretion of cholesterol-rich very low density lipoprotein. These findings show that chylomicron remnants of different fatty acid composition have differential effects on cholesterol metabolism in liver cells, and provide part of the explanation for the hyper- and hypocholesterolaemic effects of saturated and polyunsaturated fatty acids.

Research paper thumbnail of The effect of cyclic AMP analogues and glucagon on cholesteryl ester synthesis and hydrolysis in cultured hamster hepatocytes

FEBS Letters, 1993

Two cyclic AMP analogues, l-chloro cyclic AMP and 8-(4 chlorophenyltbio) cyclic AMP, were found t... more Two cyclic AMP analogues, l-chloro cyclic AMP and 8-(4 chlorophenyltbio) cyclic AMP, were found to increase the incorporation of rHJoleate into cholereryl ester in cultured hamster hapatocytes (30-40%), while incorporation into triacylglycerol was unaffected. An increase of a similar magnitude was observed in the presence of glucagon and the phosphodiesterase inhibitor, theophylline. The cyclic AMP analogues also stimulated the activity of neutral cholesteryl ester hydrolase in the cells, and this effect was mimicked by glucagon and theophylline. These results show that cyclic AMP can affect the cholesteryl ester cycle in hamster hepatocytes, and support the idea that the enzymes involved may be co-ordinately regulated.

Research paper thumbnail of A radioimmunoassay for tauro-β-muricholic acid suitable for use with isolated rat liver cells

FEBS Letters, 1983

A new radioimmunoassay which can be used to measure the amounts of tauro-&muricholic acid produce... more A new radioimmunoassay which can be used to measure the amounts of tauro-&muricholic acid produced by isolated rat hepatocytes in vitro is described. Cross reactivities of other bile acids known to be present in rat liver with the antiserum used in the assay were not sufficient to interfere with the measurement of tauro-fl-muricholic acid. Exogenous taurochenodeoxycholic acid was metabolised by isolated rat hepatocytes concurrently with the appearance of tauro-fl-muricholic acid in the cell.