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Biomedical subjects

K N Frayn

Publications and source records attributed to K N Frayn.

At least 109 records · Page 6Linked to original sources
PubMed1996

Net carbon flux across subcutaneous adipose tissue after a standard meal in normal-weight and insulin-resistant obese subjects.

OBJECTIVE: To elucidate the alterations in subcutaneous adipose tissue metabolism in obesity which affect substrate storage in the fed state, by describing as completely as possible the 'metabolic balance sheet' for adipose tissue. SUBJECTS: 13 lean people (age: 24-64 years, BMI: 19.3-29.4 kg/m2) and 9 insulin-resistant obese subjects (age: 38-57 years, BMI: 32.4-56.0 kg/m2). MEASUREMENTS: Net flux of eight major substrates and CO2 across subcutaneous adipose tissue in vivo before and after eating a standard mixed meal (3.1 MJ, 41% from fat). RESULTS: The net flux of total carbon atoms in the 8 substrates and CO2 was negative (net export from the tissue) in both groups in the fasting state. After the meal it changed rapidly to a positive balance (net substrate storage) in the control group and remained positive until 5 h, whereas in the obese group it remained negative throughout. The overall carbon balance in adipose tissue reflected predominantly the movement of fatty acids in and out of the tissue. CONCLUSIONS: The fact that fat storage failed to occur despite elevated plasma concentrations of triacylglycerol, glucose and insulin indicates an alteration in metabolic regulation at the cellular level which might be called insulin resistance. Insulin resistance of fat metabolism may be an adaptation which limits further fat deposition, but is maladaptive in terms of risk factors for atherosclerosis.

Adipose Tissue↗
PubMed1996

Release of individual fatty acids from human adipose tissue in vivo after an overnight fast.

The objective of this study was to investigate the mobilization of individual fatty acids from human subcutaneous adipose tissue in vivo. Concentrations of individual non-esterified fatty acids were measured in arterialized plasma and in the venous drainage from subcutaneous abdominal adipose tissue in eight normal subjects, after an overnight fast, and for the subsequent 6 h. Whilst the veno-arterial concentration difference for non-esterified fatty acids increased over this period, the relative proportions of different fatty acids remained constant. There was a close relationship between veno-arterial difference and arterialized concentration for the different fatty acids. The arterialized concentration of stearic acid consistently lay above the regression line drawn for unsaturated fatty acids (P = 0.001), probably reflecting lower clearance of stearic acid. The release of individual fatty acids was compared with their prevalence in adipose tissue triacylglycerol in biopsies taken from six subjects. Relative release decreased with increasing chain length, and for a given chain length increased with increasing unsaturation, in agreement with animal studies (P < 0.001 for differences in relative mobilization according to these two factors). The results suggest that the systemic plasma concentration of individual non-esterified fatty acids is determined by their release from adipose tissue, but that the relationship between release and systemic concentration for stearic acid is different from that for other fatty acids. The results confirm, in humans, differences in relative mobilization found previously in animal studies.

Adipose Tissue↗
PubMed1996

Sepsis and fat metabolism.

Sepsis is a common surgical problem which can induce profound changes in the plasma concentrations of cytokines and hormones, leading to a catabolic state. Hypertriglyceridaemia and increased fat oxidation are the main features of altered fat metabolism encountered in this state. The endogenous catabolism of sepsis can be reduced by administering exogenous lipid emulsions as a source of metabolic fuel, although the changes in lipid metabolism associated with sepsis may affect the handling of these exogenous lipids. An exciting area for future research is an examination of the ability of lipid emulsions to reduce the morbidity and mortality associated with sepsis by altering immune responses, in addition to limiting catabolism.

Adipose Tissue↗
PubMed1995

Human triacylglycerol-rich lipoprotein subfractions as substrates for lipoprotein lipase.

In order to test the hypothesis that lipoprotein lipase (LPL) acts preferentially on larger lipoprotein particles, we determined the susceptibility of triacylglycerol-rich lipoprotein (TRL) subfractions to hydrolysis by LPL in vitro. Chylomicrons (Sf > 400), very low density lipoproteins (VLDL)1 (Sf 60-400) and VLDL2 (Sf 20-60) were isolated from six subjects with a range of plasma-triacylglycerol (TAG) concentrations following an overnight fast and for up to 6 h after the consumption of a mixed meal (41% fat). The percent of TRL-TAG hydrolysed by LPL in subfractions isolated following overnight fast was VLDL1 > VLDL2 (46.8 +/- 10.2 vs. 25.9 +/- 7.4%, P = 0.006) and 3 h after the meal it was chylomicrons > VLDL1 > VLDL2 (81.0 +/- 12.6 vs. 52.8 +/- 10.2 vs. 27.7 +/- 6.2%, chylomicrons vs. VLDL1 and VLDL1 vs. VLDL2, both P < or = 0.005). The percent of VLDL1-TAG hydrolysed increased both within and between subjects as VLDL1-TAG concentrations increased. This relationship could be explained by the positive correlation observed between VLDL1-TAG and VLDL1-TAG:apolipoprotein B. In conclusion, increasing the size and TAG content of a lipoprotein particle increases its susceptibility to hydrolysis by LPL.

Adult↗
PubMed1995

Coordinated regulation of hormone-sensitive lipase and lipoprotein lipase in human adipose tissue in vivo: implications for the control of fat storage and fat mobilization.

The enzymes lipoprotein lipase (LPL, EC 3.1.1.34) and hormone-sensitive lipase (HSL, EC 3.1.1.3) apparently catalyze opposing functions in white adipose tissue: the former is concerned with fat storage, the latter with fat mobilization. We have studied their regulation in vivo in normal subjects in the postabsorptive state and after eating meals of different compositions, by measurement of arteriovenous concentration differences for triacylglycerol, non-esterified fatty acids and glycerol across a subcutaneous adipose depot. The two enzymes are regulated in a broadly reciprocal manner: in the overnight-fasted state, HSL is more active, but after a meal HSL is suppressed whilst LPL is activated. The movement of fatty acids in and out of adipose tissue appears to be driven by concentration gradients generated by regulation of these two enzymes, and also by activation, in the postprandial period, of the process of fatty acid esterification. The results show some interesting and perhaps unexpected features of metabolic regulation. Of the fatty acids generated by the action of LPL on circulating TAG, a large proportion is released directly into the venous plasma: close to 100% in the overnight-fasted state, and 50% or more at the peak of LPL action after a meal, making what appear reasonable assumptions. We suggest that this apparent 'inefficiency' of fat storage reflects the energetic cost of maintaining precise control over such a fundamental process. Although LPL is usually thought of as the enzyme regulating fat deposition, in fact the fatty acids and glycerol it releases from circulating TAG represent a substantial proportion of those released from adipose tissue, especially in the postprandial state. In addition, although HSL is considered the enzyme responsible for fat mobilization, suppression of its activity is essential to normal regulation of fat deposition. Thus, fat storage and fat mobilization during normal daily life are controlled by coordinated regulation of a number of enzymatic processes in white adipose tissue.

Adipose Tissue↗
PubMed1995

Dietary sugars and lipid metabolism in humans.

When large amounts of sugars are included in the diets of humans and other animals, alterations in concentrations of plasma lipid constituents may be observed; usually elevation of triacylglycerol concentrations and sometimes elevation of low-density-lipoprotein cholesterol and depression of high-density-lipoprotein cholesterol. These effects are not seen with amounts of sugars typical of those in the Western diet, although more information is needed on postprandial triacylglycerol concentrations, which may be affected more readily than fasting concentrations. The elevation of triacylglycerol concentrations appears to reflect both increased hepatic very-low-density-lipoprotein triacylglycerol secretion and impaired clearance. Some people are more responsive to these effects of dietary sugars than are others. Perhaps surprisingly, in many studies people with diabetes mellitus, either insulin dependent or non-insulin dependent, seem to be protected from alterations in plasma lipid concentrations brought about by large amounts of dietary sugars.

Cholesterol↗
PubMed1995

Modification and validation of a commercially available portable detector for measurement of adipose tissue blood flow.

Adipose tissue blood flow is measured from the clearance of radioactive xenon from a depot. Traditionally, a NaI detector has been used to measure the residual depot of xenon. However, this is sensitive to movement artefacts. We tested a commercially available lightweight CsI detector which can be strapped to the anterior abdominal wall. In pilot studies the CsI detector produced higher values for adipose tissue blood flow than did a conventional NaI detector. It was modified by inclusion of spacers to distance it from the skin. Flow results generated by the modified detector were similar to those generated by the NaI detector, both after an overnight fast and during the increased blood flow after a meal. Individual decay patterns generated by the CsI detector were, however, significantly smoother than those from the NaI detector.

Abdominal Muscles↗
PubMed1995

Impaired postprandial clearance of triacylglycerol-rich lipoproteins in adipose tissue in obese subjects.

Adipose tissue is an important site of clearance of circulating triacylglycerol (TAG), especially in the postprandial period. Postprandial lipemia is usually increased in obesity. We studied the extraction of TAG from plasma and TAG-rich lipoproteins (TRLs) in subcutaneous adipose tissue in 11 control and 8 obese subjects before and after a mixed meal. Clearance of plasma TAG and very low-density lipoprotein (VLDL)-TAG was decreased in the obese subjects after an overnight fast. After the meal, chylomicron-TAG extraction increased in the control group whereas VLDL-TAG clearance decreased; these changes were not seen in the obese group, in whom the VLDL particles appeared to be better able to compete with the chylomicrons for clearance by lipoprotein lipase. In the control subjects, removal of TAG from the TRL in the postprandial period was accompanied by a shift toward addition of cholesterol to the high-density lipoprotein (HDL) fraction; this was not observed in the obese subjects. We conclude that disturbed TRL-TAG clearance in adipose tissue is related both to the elevated plasma TAG concentrations and the depressed HDL-cholesterol concentrations typical of obesity.

Adipose Tissue↗
PubMed1995

Catecholamine interference with enzymatic determination of nonesterified fatty acids in two commercially available test kits.

We present evidence that catecholamines, which are commonly used to stimulate lipolysis in adipose tissue in vitro, interfere with the enzymatic determination of non-esterified fatty acid (NEFA) in two commercially available kits. Measurement of a 100 mumol/L standard with the Wako "NEFA C" test kit was 60% inhibited by 100 mumol/L norepinephrine and was completely inhibited by 100 mumol/L isoproterenol or by 1 mmol/L norepinephrine or epinephrine. Measurement with the Boehringer Mannheim "Free Fatty acids, Half-micro test" was completely inhibited by 100 mumol/L norepinephrine and was also affected by concentrations as low as 0.1 mumol/L. We propose that this effect is due to the catecholamines interfering with a step common to the two kits, the generation of hydrogen peroxide and oxidation of a chromagen; furthermore, this interference appears to be stoichiometric. We also give details of an alternative in-house method, which does not depend on the generation of hydrogen peroxide and is not affected by catecholamines.

Acyl-CoA Oxidase↗
PubMed1994

Forearm substrate utilization during exercise after a meal containing both fat and carbohydrate.

1. Whilst the provision of exogenous carbohydrate has been shown to be beneficial to endurance exercise performance, little attention has been paid to the possibility of dietary manipulation of the availability of fat. 2. Ten normal subjects were studied on two occasions: after an overnight fast (postabsorptive state) and after a meal containing 80 g of fat and 80 g of carbohydrate (fed state). Forearm substrate exchange was studied during 60 min of isometric forearm exercise (5 s contraction, 5 s relaxation). 3. In the fed state concentrations of plasma triacylglycerol (1510 +/- 150 versus 850 +/- 80 mumol/l, P < 0.01), blood ketone bodies (151 +/- 21 versus 80 +/- 10 mumol/l, P < 0.01) and plasma insulin (17 +/- 3 versus 7 +/- 1 m-units/l, P < 0.01) were elevated compared with the postabsorptive state; plasma glucose and non-esterified fatty acid concentrations were not significantly different. 4. Forearm blood flow and O2 consumption each increased about 6-fold during exercise, with no differences between the two nutritional states. The potential contribution of individual substrates to forearm O2 consumption (a calculation which is independent of blood flow) was assessed: for triacylglycerol it was significantly greater in the fed state (P < 0.01). The sum of the potential contributions of triacylglycerol, non-esterified fatty acids, glucose and ketone bodies to forearm O2 consumption was significantly greater, both before and during exercise, in the fed than in the postabsorptive state (P < 0.05), implying the sparing of endogenous (forearm) fuels. 5. These studies highlight the potential for manipulation of substrate supply during exercise by feeding meals containing both carbohydrate and fat.

Adult↗
PubMed1994

Hormonal and metabolite responses to glucose and maltodextrin ingestion with or without the addition of guar gum.

The purpose of this study was to examine the effects of ingesting water (P), a glucose solution (GL), a maltodextrin solution (Md), a glucose solution with 8% guar gum (GL+G), and a maltodextrin solution with 8% guar gum (Md+G), on the hormonal and metabolite responses during cycling, and on subsequent time to exhaustion. Five male subjects undertook five 90 min rides on a bicycle ergometer at an exercise intensity corresponding to 65% VO2max after having ingested 1 g.kg-1 body weight of the test product in 400 ml of water immediately before the exercise. Blood samples were taken during the trials for analyses of adrenaline, noradrenaline, insulin, glucagon, glucose, lactate and non-esterified fatty acids (NEFA). Respiratory measures were also undertaken during the trials for the determination of oxygen consumption (VO2) and respiratory exchange ratio (RER), from which the carbohydrate oxidation rates were calculated. Rates of perceived exertion (RPE) were also assessed. Ten minutes after the 90 min ride, subjects exercised to volitional exhaustion at an exercise intensity of 75% VO2max. ANOVA revealed that there were significant differences between the treatments for adrenaline (p < 0.01), insulin (p < 0.05), glucose (p < 0.01), lactate (p < 0.01), NEFA (p < 0.01), RER (p < 0.001) and carbohydrate oxidation rate (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗