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Luc Tappy

Publications and source records attributed to Luc Tappy.

35 records · Page 2Linked to original sources
PubMed2004

Metabolic effects of caffeine in humans: lipid oxidation or futile cycling?

BACKGROUND: Caffeine ingestion stimulates both lipolysis and energy expenditure. OBJECTIVES: Our objectives were to determine whether the lipolytic effect of caffeine is associated with increased lipid oxidation or futile cycling between triacylglycerol and free fatty acids (FFAs) and whether the effects of caffeine are mediated via the sympathetic nervous system. DESIGN: Respiratory exchange and [1-(13)C]palmitate were used to trace lipid oxidation and FFA turnover in 8 healthy, young men for 90 min before and 240 min after ingestion of placebo, caffeine (10 mg/kg), or caffeine during beta-adrenoceptor blockade. RESULTS: During fasting conditions, there were few differences in measured variables between the 3 tests. During steady state conditions (last hour of the test) after ingestion of caffeine, lipid turnover increased 2-fold (P < 0.005), and the mean (+/-SEM) thermic effect was 13.3 +/- 2.2% (P < 0.001), both of which were greater than after ingestion of placebo or caffeine during beta-adrenoceptor blockade. After ingestion of caffeine, oxidative FFA disposal increased 44% (236 +/- 21 to 340 +/- 16 micro mol/min), whereas nonoxidative FFA disposal increased 2.3-fold (455 +/- 66 to 1054 +/- 242 micro mol/min; P < 0.01). In postabsorptive conditions, 34% of lipids were oxidized and 66% were recycled. Caffeine ingestion increased energy expenditure 13% and doubled the turnover of lipids, of which 24% were oxidized and 76% were recycled. beta-Adrenoceptor blockade decreased, but did not inhibit, these variables. CONCLUSIONS: Many, but not all, of the effects of caffeine are mediated via the sympathetic nervous system. The effect of caffeine on lipid mobilization in resting conditions can be interpreted in 2 ways: lipid mobilization alone is insufficient to drive lipid oxidation, or large increments in lipid turnover result in small increments in lipid oxidation.

Adrenergic beta-Antagonists↗
PubMed2004

Relationship between stress, inflammation and metabolism.

PURPOSE OF REVIEW: Various threatening stimuli, such as pain, low blood pressure, or infection, elicit a set of neuroendocrine responses that include an increased secretion of catecholamines and glucocorticoid from the adrenal gland and activation of the sympathetic nervous system. These hormonal secretions allow a "fight or flight" response by mobilizing endogenous substrate. They also exert anti-insulin actions, and may in the long term induce a state of insulin resistance. In addition, stress stimulates inflammatory mediators in mononuclear cells. Given the possible role of low-grade inflammation in chronic metabolic disorders, this suggests that stress may be a factor in the development of insulin resistance and the metabolic syndrome. RECENT FINDINGS: Studies reviewed in this article cover: (1) the metabolic and haemodynamic effects of stress in healthy and insulin-resistant individuals; (2) the relationship between stress and inflammation and the role of the autonomic nervous system; and (3) some factors known to modulate the neuroendocrine responses to stress. Future perspectives, together with some hints regarding the role of neurotrophins such as brain-derived neurotrophic factor, are delineated. SUMMARY: Recent work performed in the field has indicated that stress may be a significant factor in the pathogenesis of metabolic disorders. Nutritional intervention or pharmacological agents targeted at modulating stress should be investigated.

Cytokines↗
PubMed2004

Metabolic consequences of overfeeding in humans.

PURPOSE OF REVIEW: Overfeeding leads to obesity and metabolic disorders, including impaired glucose homeostasis, lipid disorders, and hepatic steatosis. The consequences of standardized overfeeding on body weight have shown, however, considerable interindividual variability, which suggests that it also leads to adaptative changes in energy expenditure, in some individuals at least. The present review is mainly focused on the recent developments regarding the effects of overfeeding on energy expenditure. RECENT FINDINGS: Individuals who gain the less body weight during overfeeding are those who experience a greater increase in total energy expenditure. This increase in energy expenditure has been attributed to stimulation of nonexercise physical activity. Recent developments regarding adaptative increases in physical activity are critically reviewed. Overfeeding also alters the pathways used for carbohydrate storage after a glucose load, by increasing de-novo lipogenesis in the liver and adipose tissue at the expense of glycogen storage. The sympathetic nervous system is a good candidate for energy expenditure increase during overfeeding. The increases in energy expenditure observed during acute stimulation of the sympathetic nervous system were however found to be unaltered by short-term overfeeding. SUMMARY: The mechanisms by which some individuals protect themselves against body weight gain remain poorly understood. Nonvoluntary physical activity may allow one to increase energy expenditure during overfeeding, and may therefore constitute a regulatory factor in body weight control. The biological determinant of spontaneous, nonvoluntary physical activity, however, remains to be investigated.

Adaptation, Physiological↗
PubMed2003

Effect of carbohydrate overfeeding on whole body and adipose tissue metabolism in humans.

OBJECTIVE: To evaluate the effect of a 4-day carbohydrate overfeeding on whole body net de novo lipogenesis and on markers of de novo lipogenesis in subcutaneous adipose tissue of healthy lean humans. RESEARCH METHODS AND PROCEDURES: Nine healthy lean volunteers (five men and four women) were studied after 4 days of either isocaloric feeding or carbohydrate overfeeding. On each occasion, they underwent a metabolic study during which their energy expenditure and net substrate oxidation rates (indirect calorimetry), and the fractional activity of the pentose-phosphate pathway in subcutaneous adipose tissue (subcutaneous microdialysis with 1,6(13)C2,6,6(2)H2 glucose) were assessed before and after administration of glucose. Adipose tissue biopsies were obtained at the end of the experiments to monitor mRNAs of key lipogenic enzymes. RESULTS: Carbohydrate overfeeding increased basal and postglucose energy expenditure and net carbohydrate oxidation. Whole body net de novo lipogenesis after glucose loading was markedly increased at the expense of glycogen synthesis. Carbohydrate overfeeding also increased mRNA levels for the key lipogenic enzymes sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase. The fractional activity of adipose tissue pentose-phosphate pathway was 17% to 22% and was not altered by carbohydrate overfeeding. DISCUSSION: Carbohydrate overfeeding markedly increased net de novo lipogenesis at the expense of glycogen synthesis. An increase in mRNAs coding for key lipogenic enzymes suggests that de novo lipogenesis occurred, at least in part, in adipose tissue. The pentose-phosphate pathway is active in adipose tissue of healthy humans, consistent with an active role of this tissue in de novo lipogenesis.

Adipose Tissue↗
PubMed2003

Metabolic adaptations to dexamethasone-induced insulin resistance in healthy volunteers.

OBJECTIVE: Insulin resistance is observed in individuals with normal glucose tolerance. This indicates that increased insulin secretion can compensate for insulin resistance and that additional defects are involved in impaired glucose tolerance or type 2 diabetes. The objective of this study was to evaluate a procedure aimed at assessing the compensatory mechanisms to insulin resistance. RESEARCH METHODS AND PROCEDURES: Eight healthy nonobese female patients were studied on two occasions, before and after administration of 2 mg/d dexamethasone for 2 days during a two-step hyperglycemic clamp. Insulin secretion was assessed from plasma insulin concentrations. Insulin sensitivity was assessed from the ratio of whole-body glucose use (6,6 (2)H(2) glucose) to plasma insulin concentrations. This procedure is known to induce a reversible impairment of glucose tolerance and insulin resistance. RESULTS: In all subjects, dexamethasone induced a decrease in insulin sensitivity and a proportionate increase in first-phase insulin secretion and in insulin concentrations at both steps of glycemia. The resulting hyperinsulinemia allowed the restoration of normal whole-body glucose uptake and the suppression of plasma free fatty acids and triglycerides. In contrast, the suppression of endogenous glucose production was impaired after dexamethasone (p < 0.01). DISCUSSION: Increased insulin secretion fully compensates dexamethasone-induced insulin resistance in skeletal muscle and adipose tissue but not in the liver. This suggests that failure to overcome hepatic insulin resistance can impair glucose tolerance. The compensatory insulin secretion in response to insulin resistance can be assessed by means of a hyperglycemic clamp after a dexamethasone challenge.

Adult↗
PubMed2003

Assessment of adipose tissue metabolism by means of subcutaneous microdialysis in patients with sepsis or circulatory failure.

To evaluate the role of adipose tissue in the metabolic stress response of critically ill patients, the release of glycerol and lactate by subcutaneous adipose tissue was assessed by means of microdialysis in patients with sepsis or circulatory failure and in healthy subjects. Patients with sepsis had lower plasma free fatty acid concentrations and non-significant elevations of plasma glycerol concentrations, but higher adipose-systemic glycerol concentrations gradients than healthy subjects or patients with circulatory failure, indicating a stimulation of subcutaneous adipose lipolysis. They also had a higher lipid oxidation. Lipid metabolism (adipose-systemic glycerol gradients, lipid oxidation) was not altered in patients with circulatory failure. These observations highlight major differences in lipolysis and lipid utilization between patients with sepsis and circulatory failure. Hyperlactataemia was present in both groups of patients, but the adipose-systemic lactate concentration gradient was not increased, indicating that lactate production by adipose tissue was not involved. This speaks against a role of adipose tissue in the development of hyperlactataemia in critically ill patients.

Adipose Tissue↗
PubMed2003

Labeled acetate to assess intestinal absorption in critically ill patients.

OBJECTIVE: To compare the absorption of carbon-13(13C) acetate-enriched nutrients with D-xylose absorption. DESIGN: Prospective cohort observational study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: A total of 24 critically ill patients requiring enteral nutritional support. INTERVENTION: The patients were divided into three groups according to the route of 13C acetate administration: 1) gastric, 2) jejunal, and 3) intravenous. D-xylose was administered via the same route as enteral nutrition. MEASUREMENTS AND MAIN RESULTS: 13C acetate absorption and oxidation were reflected by pulmonary 13CO2 excretion. Breath 13CO2 isotopic enrichment was measured by mass spectrometry. 13C acetate absorption was rapid, and D-xylose absorption was depressed in all three groups, compared with the normal values (p <.0001). Breath CO isotopic enrichment was similar after intravenous and jejunal administration but slightly delayed during the first 240 mins after gastric administration (p <.01). Enteral feeding was well tolerated: mean energy delivery amounted to 77%, 88%, and 86% of measured resting energy expenditure on days 1-3. CONCLUSIONS: Gastric and jejunal 13C acetate are rapidly absorbed in critically ill surgical patients requiring enteral nutrition, contrasting with a depressed or delayed D-xylose absorption. 13CO2 recovery kinetics was similar after jejunal or intravenous 13C acetate and slightly depressed after gastric administration. Further studies are required to determine the value of labeled nutrients to assess gastric emptying and intestinal absorption.

Acetates↗
PubMed2002

Hepatic insulin resistance in obese non-diabetic subjects and in type 2 diabetic patients.

OBJECTIVE: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial. RESEARCH METHODS AND PROCEDURES: To estimate their hepatic insulin sensitivity, we measured the rate of exogenous insulin infusion required to maintain mildly elevated glycemia in obese patients with type 2 diabetes, obese non-diabetic patients, and lean control subjects during constant infusions of somatostatin and physiological low-glucagon replacement infusions. To account for differences in insulin concentrations among the three groups of subjects, an additional protocol was also performed in healthy lean subjects with higher insulin infusion rates and exogenous dextrose infusion. RESULTS: The insulin infusion rate required to maintain glycemia at 8.5 mM was increased 4-fold in obese patients with type 2 diabetes and 1.5-fold in obese non-diabetic patients. The net endogenous glucose production (measured with 6,6-(2)H(2)-glucose) and total glucose output (measured with 2-(2)H(1)-glucose) were approximately 30% lower in the patients than in the lean subjects. Net endogenous glucose production and total glucose output were both markedly increased in both groups of obese patients compared with lean control subjects during hyperinsulinemia. DISCUSSION: Our data indicate that both obese non-diabetic and obese type 2 diabetic patients have a blunted suppressive action of insulin on glucose production, indicating hepatic and renal insulin resistance.

Adult↗
PubMed2002

Metabolic effects of mental stress during over- and underfeeding in healthy women.

OBJECTIVE: To assess the short-term consequences of carbohydrate or fat overfeeding or of food restriction on the metabolic effects of mental stress in healthy lean women. RESEARCH METHODS AND PROCEDURES: The effects of a sympathetic activation elicited by mental stress were evaluated in a group of healthy women after standardized isocaloric feeding (ISO) or after a 3-day overfeeding with 40% excess calories as either carbohydrate overfeeding (CHO OF) or fat overfeeding (FAT OF). Oxygen consumption rate (VO(2)) was measured as an index of energy expenditure, and subcutaneous glycerol concentrations were monitored with microdialysis. The same measurements were performed in another group of healthy women after ISO and after a 3-day period of underfeeding with a protein sparing modified fast (UF). RESULTS: In all conditions, mental stress significantly increased heart rate, blood pressure, plasma norepinephrine and epinephrine concentrations, and VO(2), and produced a nonsignificant increase in subcutaneous glycerol concentrations. CHO OF and FAT OF did not alter the effects of mental stress on VO(2) and subcutaneous glycerol concentrations. In contrast, UF increased basal VO(2) but significantly reduced its stimulation by mental stress. UF also enhanced the increase in subcutaneous glycerol concentrations during mental stress. DISCUSSION: UF reduces the stimulation of energy expenditure and enhances lipolysis during sympathetic activation. These adaptations may be involved in mobilization of endogenous fat while limiting weight loss. In contrast, short-term overfeeding fails to alter the sympathetic control of energy expenditure and lipolysis.

Adult↗
PubMed2002

Measurement of the whole body clearance of infused glycerol as a test of liver function after major hepatectomy.

Major liver resection can be used in the treatment of liver cancer. The functional capacity of liver parenchyma needs to be evaluated preoperatively because it conditions the outcome. We assessed whether the whole body clearance of glycerol, a substrate essentially metabolized in liver cells, may be suitable as a simple test of liver function. Seven patients after major hepatectomy, six patients after colectomy and 12 healthy subjects were studied. Patients were investigated on the first day after surgery. All participants were studied during a 150-min basal period followed by a 120-min infusion of 16 mumol kg-1 min-1 13C-labelled glycerol. Whole body glycerol clearance was calculated from the change in plasma glycerol concentration. Whole body glucose production was measured with 6,6 2H2 glucose infused as a tracer in the basal state and during glycerol infusion. In addition, 13C glucose synthesis was monitored to quantitate gluconeogenesis from glycerol. Patients after liver resection had higher plasma glycerol concentrations and lower whole body glycerol clearance than healthy subjects and patients after colectomy. They also had higher plasma glucagon concentrations. Their fasting glucose production was mildly elevated in the fasting state and did not change after glycerol infusion, indicating a normal hepatic autoregulation of glucose production. These results indicate that whole body glycerol clearance can be simply determined from plasma glycerol concentrations during exogenous glycerol infusion. It is significantly reduced in patients after major hepatectomy, suggesting that it constitutes a sensitive test of hepatic function. Its use as a preoperative testing procedure remains to be evaluated.

Adult↗
PubMed2002

Microdialysis in the intensive care unit: a novel tool for clinical investigation or monitoring?

Microdialysis is a minimally invasive tool that allows us to gain insight into metabolism at the tissue level. In human investigations, it can be safely performed in the brain (neurosurgical patients), skeletal muscle and adipose tissue. Basically, the technique allows interstitial concentrations of small solutes to be evaluated. Several limitations of the method and possible ways to circumvent them are indicated. Recent technical developments are reviewed. At present, this method is rarely used in metabolic monitoring of critically ill patients, but its potential applications are highlighted.

Critical Care↗
PubMed2002

Effects of fatty acids on exercise plus insulin-induced glucose utilization in trained and sedentary subjects.

Fatty acids are known to decrease insulin-mediated glucose utilization in humans, both at rest and during exercise. To evaluate the effect of endurance training in this process, we infused lipids or saline in groups of sedentary and highly trained subjects. Whole body glucose utilization and substrate oxidation were monitored during a 2.5-h hyperinsulinemic clamp. During the last 30 min, a cycling exercise was superimposed. During hyperinsulinemia at rest, whole body glucose utilization and glucose oxidation were higher in trained subjects than in sedentary subjects. Compared with the control experiments with the antilipolytic agent acipimox, lipid infusion stimulated lipid oxidation to the same extent in trained as in sedentary subjects. It reduced whole body glucose utilization by 37% in trained and by 41% in sedentary subjects. During exercise, lipid infusion increased more lipid oxidation in trained than in sedentary subjects and reduced whole body glucose utilization by 43 +/- 4% in trained and by 22 +/- 4% in sedentary subjects (P < 0.01). The present data indicate that lipid infusion has similar effects on lipid oxidation and whole body glucose utilization during hyperinsulinemia at rest in trained and sedentary subjects. During exercise, however, it increases more lipid oxidation and produces a more important reduction in glucose utilization in trained than in sedentary subjects. These results suggest that endurance training enhances the inhibitory effect of lipids on whole body glucose metabolism during exercise.

Adult↗
PubMed2000

Autoregulation of Glucose Production.

Glucose itself regulates endogenous glucose production independently of changes in glucoregulatory hormones. In addition, acute stimulation of gluconeogenesis does not increase net glucose production. This indicates autoregulation of glucose production. Glucokinase plays a role in this process by allowing hepatic glucose sensing.

Journal Article↗
PubMedDate not supplied

Serum paracetamol concentration: an alternative to X-rays to determine feeding tube location in the critically ill.

BACKGROUND: Placement of enteral feeding tubes is an important clinical issue. Previous studies suggest that paracetamol absorption is very fast after jejunal administration. The aim was to determine whether paracetamol serum concentration measured by immunoassay can determine the tip position of the feeding tube. METHODS: Thirty-three critically ill patients requiring enteral nutrition with either gastric or post-pyloric feeding tubes were enrolled prospectively in the surgical intensive care unit of a university hospital. Paracetamol was administered in the feeding tube (15 mg/kg) after a baseline blood sample (T0). Thereafter, 8 blood samples were taken between 2.5 and 240 minutes. Paracetamol was analyzed using an automated homogenous immunoassay. RESULTS: The patients did not differ with respect to age or severity of disease. Peak paracetamol concentrations were significantly higher after post-pyloric administration with 42.6 +/- 13.5 versus 20.5 +/- 7.5 mg/L (p < .0001). Time-to-peak paracetamol concentration was significantly shorter with post-pyloric tubes (median, 5 versus 60 minutes; p < .0001). The receiver operating characteristic (ROC) curves showed the highest sensitivity and specificity at 5 minutes with 94.1% and 100%, respectively, for discriminating between gastric and post-pyloric location. CONCLUSIONS: Because of paracetamol's rapid absorption after jejunal administration, the test seems to be a safe and inexpensive alternative to X-ray control for assessment of the enteral feeding tube location. Its value in clinical practice remains to be established.

Acetaminophen↗