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Biomedical subjects

K N Frayn

Publications and source records attributed to K N Frayn.

At least 73 records · Page 4Linked to original sources
PubMed1998

Lipoprotein lipase and the disposition of dietary fatty acids.

Lipoprotein lipase (EC 3.1.1.34; LPL) is a key enzyme regulating the disposal of lipid fuels in the body. It is expressed in a number of peripheral tissues including adipose tissue, skeletal and cardiac muscle and mammary gland. Its role is to hydrolyse triacylglycerol (TG) circulating in the TG-rich lipoprotein particles in order to deliver fatty acids to the tissue. It appears to act preferentially on chylomicron-TG, and therefore may play a particularly important role in regulating the disposition of dietary fatty acids. LPL activity is regulated according to nutritional state in a tissue-specific manner according to the needs of the tissue for fatty acids. For instance, it is highly active in lactating mammary gland; in white adipose tissue it is activated in the fed state and suppressed during fasting, whereas the reverse is true in muscle. Such observations have led to the view of LPL as a metabolic gatekeeper, especially for dietary fatty acids. However, closer inspection of its action in white adipose tissue reveals that this picture is only partially true. Normal fat deposition in adipose tissue can occur in the complete absence of LPL, and conversely, if LPL activity is increased by pharmacological means, increased fat storage does not necessarily follow. LPL appears to act as one member of a series of metabolic steps which are regulated in a highly coordinated manner. In white adipose tissue, it is clear that there is a major locus of control of fatty acid disposition downstream from LPL. This involves regulation of the pathway of fatty acid uptake and esterification, and appears to be regulated by a number of factors including insulin, acylation-stimulating protein and possibly leptin.

Adipose Tissue↗
PubMed1998

Peripheral fat metabolism during infusion of an exogenous triacylglycerol emulsion.

OBJECTIVE: To test the hypothesis that intravenous infusion of lipid would bring about changes in adipose tissue metabolism, which would tend to spare net fat mobilization, and to attempt to identify the mediators of such responses. DESIGN: The triacylglycerol (TG) emulsion, Intralipid, was infused and metabolic changes in subcutaneous adipose tissue and forearm muscle were assessed by measurements of arterio-venous differences. SUBJECTS: Six normal male subjects aged 21-37 y, with body mass index (BMI) 23.0-25.9 kg/m2. RESULTS: Plasma TG and non-esterified fatty acid (NEFA) concentrations rose during infusion as expected. The rise in systemic plasma NEFA concentration occurred despite decreased NEFA release from adipose tissue. Intralipid infusion resulted in a suppression of intracellular lipolysis in adipose tissue, by mechanisms which are not clear. Plasma leptin concentrations, measured in a search for the regulator of lipolysis, showed consistent leptin release from adipose tissue which did not change significantly with time. CONCLUSION: The suppression of intracellular lipolysis in adipose tissue during Intralipid infusion is a new observation and may reflect a novel mechanism for regulation of fat storage.

3-Hydroxybutyric Acid↗
PubMed1998

The effect of triacylglycerol-fatty acid positional distribution on postprandial metabolism in subcutaneous adipose tissue.

We hypothesized that fatty acids at the sn-2 position of chylomicron triacylglycerol are preferentially released into the venous plasma (rather than being taken up and stored in the adipocytes) after hydrolysis by lipoprotein lipase (EC 3.1.1.34) in adipose tissue. Arteriovenous differences across adipose tissue were studied in eight healthy subjects on two occasions for 6 h after ingestion of different structured triacylglycerols rich in palmitic acid either at the sn-2 or the sn-1,3 positions. In particular the specific fatty acids making up lipoprotein fractions and plasma non-esterified fatty acids were analysed. After the different meals there were no differences between either postprandial arterialized or venous plasma metabolite concentrations. Chylomicron triacylglycerol extraction in adipose tissue was the same following the two types of fat. There was no difference between the specific fatty acid composition of the postprandial non-esterified fatty acid release from adipose tissue after ingestion of the two triacylglycerols, indicating that there was no preferential release of a saturated fatty acid at the sn-2 position.

Adipose Tissue↗
PubMed1998

Rapid chylomicron appearance following sequential meals: effects of second meal composition.

Previous studies have noted the presence of an early postprandial peak in plasma triacylglycerol concentrations following successive fat-rich meals. An earlier study has shown that the triacylglycerol in this early peak originates from a previous meal. The present study was performed to investigate the effects of different second meals on the plasma triacylglycerol response. Six healthy subjects were studied on four occasions each. At 5 h following a fat-rich breakfast they ingested one of the following in a balanced design: a fat-rich meal, a low-fat meal, water or nothing by mouth. Blood samples were taken for 2.5 h following the second meal. An early peak in chylomicron and plasma triacylglycerol concentrations was seen following both low-fat and fat-rich second meals but not following water. During studies investigating postprandial lipaemia, further meals must be avoided, even if they contain no fat, although water may be allowed.

Adult↗
PubMed1998

Functional food science and substrate metabolism.

The present review addresses the role of food constituents in the aetiology of metabolic conditions and chronic diseases, mostly related to energy metabolism and substrate regulation, such as obesity and non-insulin-dependent diabetes mellitus. Second, attention is paid to malnutrition, a major cause of mortality and morbidity in developing countries, which may be a cause of concern in Europe because of the increasing number of elderly people in the population. Finally, the role of diet during exercise, a condition of enormous substrate demands, is evaluated. Based on a critical evaluation of the existing knowledge in the literature, implications for future research in relation to functional foods are discussed.

Adolescent↗
PubMed1998

Adipose tissue metabolism in the postprandial period: microdialysis and arteriovenous techniques compared.

We investigated whether two different methods of studying metabolism in adipose tissue, microdialysis and the arteriovenous technique, produced comparable results during the postprandial period. Interstitial glycerol concentrations measured by microdialysis are usually used as an index of intracellular lipolysis, and it is not known whether they also reflect the intravascular action of lipoprotein lipase in the postprandial period. The two techniques were compared in 10 healthy subjects fed mixed meals. Interstitial glycerol concentrations reflected those measured in adipose tissue venous plasma. However, the calculation of the rate of glycerol release from adipose tissue using the microdialysis data differed systematically from that using arteriovenous difference measurement. The former method gave, on average, 40% lower values than the latter one. The difference is probably due to the assumptions that had to be made for the calculation of glycerol release. The two techniques have complementary places in the study of postprandial adipose tissue metabolism, with microdialysis reflecting intracellular hormone-sensitive lipase action rather than intravascular lipoprotein lipase.

Adipose Tissue↗
PubMed1998

Metabolic and performance responses during endurance exercise after high-fat and high-carbohydrate meals.

We studied the effects of preexercise meal composition on metabolic and performance-related variables during endurance exercise. Eight well-trained cyclists (maximal oxygen uptake 65.0 to 83.5 ml . kg-1 . min-1) were studied on three occasions after an overnight fast. They were given isoenergetic meals containing carbohydrate (CHO), protein (P), and fat (F) in the following amounts (g/70 kg body wt): high-carbohydrate meal, 215 CHO, 26 P, 3 F; high-fat meal, 50 CHO, 14 P, 80 F. On the third occasion subjects were studied after an overnight fast. Four hours after consumption of the meal, subjects started exercise for 90 min at 70% of their maximal oxygen uptake, followed by a 10-km time trial. The high-carbohydrate meal compared with the high-fat meal resulted in significant decreases (P < 0.05) in blood glucose, plasma nonesterified fatty acids, plasma glycerol, plasma chylomicron-triacylglycerol, and plasma 3-hydroxybutyrate concentrations during exercise. This was accompanied by an increase in plasma insulin (P < 0.01 vs. no meal), plasma epinephrine, and plasma growth hormone concentrations (each P < 0.05 vs. either of the other conditions) during exercise. Despite these large differences in substrate and hormone concentrations in plasma, substrate oxidation during the 90-min exercise period was similar in the three trials, and there were no differences in performance on the time trial. These results suggest that, although the availability of fatty acids and other substrates in plasma can be markedly altered by dietary means, the pattern of substrate oxidation during endurance exercise is remarkably resistant to alteration.

Adult↗
PubMed1998

Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue.

Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P < 0.001); on the other occasion (control study) no intervention was made. Lipolysis in the s.c. adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P < 0.01) and blood glycerol concentrations (P < 0.05), with an increase in systemic glycerol appearance (P < 0.05). However, in s.c. abdominal adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P < 0.05) and reduced NEFA efflux (P < 0.05). This reduction was attributable to decreased intracellular lipolysis (P < 0.05), reflecting decreased hormone-sensitive lipase action in this adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P < 0.05), but without a significant change in the local extraction of TAG (presumed to reflect the action of adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

3-Hydroxybutyric Acid↗
PubMed1998

Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period.

The objective of this study was to determine whether Acylation Stimulating Protein (ASP) is generated in vivo by human adipose tissue during the postprandial period. After a fat meal, samples from 12 subjects were obtained (up to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous adipose tissue bed were calculated. The data demonstrate that ASP is produced in vivo (positive V-A gradient) With maximal production at 3-5 h postprandially. The plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient. It increased substantially after 3 h and remained prominent until the final time point. There was, therefore, a close temporal coordination between ASP generation and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid (NEFA) had an early (1-2 h) postprandial change. Fatty acid incorporation into adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty acid (NEFA) differences postprandially. FIAT was negative during the first hour, implying net fat mobilization. FIAT then became increasingly positive, implying net fat deposition, and overall followed the same time course as ASP and TAG clearance. There was a direct positive correlation between total ASP production and total FIAT (r = 0.566, P < 0.05). These data demonstrate that ASP is generated in vivo by human adipocytes and that this process is accentuated postprandially, supporting the concept that ASP plays an important role in clearance of TAG from plasma and fatty acid storage in adipose tissue.

Adipose Tissue↗
PubMed1998

Acute effect of fructose on postprandial lipaemia in diabetic and non-diabetic subjects.

We investigated whether the potentiation of postprandial lipaemia by fructose occurs in both non-diabetic subjects and those with non-insulin-dependent diabetes mellitus. Six non-diabetic and six diabetic subjects were studied on two occasions. They were given a meal containing 1 g fat/kg body weight with, on one occasion, 0.75 g fructose/kg body weight, on the other occasion 0.75 g starch/kg body weight. In both groups, plasma glucose and insulin concentrations rose more after starch than after fructose. At 1-2 h after the meal, plasma non-esterified fatty acid concentrations were suppressed more after fructose than after starch, but later they rose more after fructose than after starch. Plasma triacylglycerol concentrations rose more slowly after fructose, but were considerably higher than those after starch from 4-6 h after the meal. There were no differences in post-heparin plasma lipoprotein lipase (EC 3.1.1.34) activity at the end of the test. The potentiation of postprandial lipaemia by fructose was positively related to the fasting plasma insulin concentration, suggesting that insulin-resistant subjects are more prone to this effect. We conclude that the potentiation of postprandial lipaemia by fructose is seen in both diabetic and non-diabetic subjects. Our results suggest that alterations in the dynamics of plasma non-esterified fatty acids might underlie the effects of fructose on triacylglycerol metabolism.

Adult↗
PubMed1998

Lipoprotein lipase transport in plasma: role of muscle and adipose tissues in regulation of plasma lipoprotein lipase concentrations.

Lipoprotein lipase (LPL) is synthesized in tissues involved in fatty acid metabolism such as muscle and adipose tissue. LPL is also found in the circulation, but is mostly lipolytically inactive. The proportion of active circulating LPL increases after a fatty meal. We investigated the release of active and inactive LPL from adipose tissue and muscle in the fasting and postprandial states. Arteriovenous concentration gradients of LPL across adipose tissue and forearm muscle were measured in male subjects before and after a fat-rich meal (n = 7) and before and during infusion of a triacylglycerol emulsion (Intralipid) (n = 6). Plasma LPL activity rose after the meal and more so during Intralipid infusion. Plasma LPL mass (>95% inactive LPL) increased after the meal but decreased after Intralipid infusion. In the fasting state (n = 13) muscle efflux of LPL activity was 0.263 +/- 0.098 mU/min per 100 ml of muscle tissue whereas there was an influx of LPL activity to adipose tissue of 0.085 +/- 0.100 mU/min per 100 g of adipose tissue (P < 0. 02 muscle vs. adipose tissue). Similarly in the postprandial state only muscle released LPL activity. Both tissues released LPL mass. In the fasting state efflux was 17.8 +/- 8.8 ng/min per 100 ml muscle and 55.2 +/- 21.3 ng/min per 100 g of adipose tissue (P < 0. 05 muscle vs. adipose tissue). Release of LPL, either active or inactive, was not correlated with levels of non-esterified fatty acids or plasma triacylglycerol. In conclusion, there is a substantial release of LPL from adipose tissue and muscle, most of which is inactive. A small proportion of active LPL seems to be redistributed from muscle to adipose tissue.

Adipose Tissue↗
PubMed1997

Very-low-density lipoprotein subfraction composition and metabolism by adipose tissue.

Lipoprotein lipase (LPL) plays a pivotal role in very-low-density lipoprotein (VLDL) metabolism. Within the circulation, the VLDL population is heterogeneous with respect to both size and composition. Several studies have investigated the action of LPL in vitro on different VLDL subfractions, but little is known of the action of LPL in vivo. To investigate this, arterial and adipose tissue venous plasma samples were obtained from 16 normal male healthy volunteers (aged 24.4 +/- 1.8 years; body mass index, 23.5 +/- 0.7 kg.m-2) following an overnight fast. VLDL subfractions were isolated (VLDL1 of Sf 60 to 400 and VLDL2 of Sf 20 to 60) and characterized in terms of triacylglycarol (TAG) and apolipoprotein (apo) B, E, CI, CII, and CIII content. The apolipoprotein content of VLDL1 differed from that of VLDL2: the VLDL2 fraction contained significantly more apo B (0.018 +/- 0.004 v 0.011 +/- 0.003 mumol.L-1, p = .001) but the ratios of TAG:apo B and apo CI:B, and CII:B, and CIII:B were significantly higher in VLDL1 (48,200 +/- 7,980 v 13,860 +/- 2,420, 22.7 +/- 5.5 v 12.5 +/- 2.2, 45.0 +/- 6.3 v 14.9 +/- 2.0, and 0.434 +/- 0.077 v 0.357 +/- 0.054, respectively, molar ratios, all P < .05). The venous blood draining an adipose tissue depot contained less VLDL1-TAG than arterial blood (328 +/- 68 v 381 +/- 83 mumol.L-1, respectively, P < .01), whereas VLDL2-TAG exhibited an opposite tendency (199 +/- 46 v 172 +/- 31 mumol.L-1, NS). Concentrations of VLDL1-apo B, -apo CII, and -apo CIII were significantly less in adipose tissue venous blood compared with arterial blood (0.011 +/- 0.004 v 0.013 +/- 0.004, 0.38 +/- 0.08 v 0.43 +/- 0.10, and 1.33 +/- 0.35 v 1.58 +/- 0.38 mumol.L-1, respectively, all P < .05). These studies demonstrated novel differences in VLDL1 and VLDL2 in terms of composition and metabolism by human adipose tissue LPL in vivo.

Adipose Tissue↗
PubMed1997

Metabolic responses to isoenergetic meals containing different proportions of carbohydrate and fat.

The purpose of the present study was to investigate the interrelationship between carbohydrate and fat metabolism at rest after isoenergetic meals of varying proportions of carbohydrate and fat. Eight physically-active subjects (BMI 18.1-23.4 kg/m2) were studied at rest on three occasions after an overnight fast. In a balanced design they were given meals containing carbohydrate, protein and fat in the following amounts respectively (g/70 kg body weight): meal 1 121, 16, 48; meal 2 70, 16, 70; meal 3 50, 14, 80. All meals were isoenergetic, containing 4.0 MJ/70 kg body weight, and were of similar appearance. In addition, on a fourth occasion five of the eight subjects consumed meal 4 (g/70 kg body weight): carbohydrate 0, protein 0, fat 108. Blood samples were taken before eating the meal and at intervals following the meal to determine metabolic and hormonal responses. Energy expenditure and substrate oxidation were measured by indirect calorimetry and balance was calculated over the 5 h postprandial period. The incremental areas under the time curves for fat oxidation were greatest after meals 3 and 4 (P < 0.05), whereas incremental areas under the carbohydrate oxidation v. time curves were relatively reduced after these two meals (P < 0.05). This was accompanied by lesser suppression of plasma non-esterified fatty acid concentrations (P < 0.001) and reduced plasma insulin concentrations (P < 0.001) following these meals. Energy balance was almost identical after the three isoenergetic meals. In contrast, there was an inverse relationship between carbohydrate and fat balance following these meals, with carbohydrate balance decreasing as carbohydrate intake decreased and fat balance increasing as fat intake increased. We conclude that there is a close interrelationship between carbohydrate and fat metabolism following isoenergetic meals in resting subjects.

Adult↗