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Biomedical subjects

E E Blaak

Publications and source records attributed to E E Blaak.

At least 37 records · Page 2Linked to original sources
PubMed2001

beta-Adrenoceptor-mediated thermogenesis and lipolysis in patients with chronic obstructive pulmonary disease.

The present study investigated whether development or maintenance of a relatively increased fat mass in normal-weight patients with chronic obstructive pulmonary disease (COPD), despite periods of weight loss, may be related to impaired beta-adrenoceptor-mediated responses in lipid utilization and thermogenesis. Nine COPD patients and nine healthy controls (body mass index: 23.0 +/- 1.3 vs. 23.8 +/- 0.6 kg/m2, not significant; fat mass: 19.0 +/- 2.1 vs. 11.9 +/- 1.5 kg, P < 0.01) received consecutive 30-min infusions of 6, 12, and 24 ng x kg fat free mass(-1) x min(-1) isoproterenol. During beta-adrenergic stimulation, nonesterified fatty acid levels increased significantly less in COPD patients (P < 0.001). Respiratory exchange ratio decreased similarly in both groups, indicating a similar change in the rate of lipid to carbohydrate oxidation. Energy expenditure increased similarly in both groups during beta-adrenergic stimulation. However, because plasma isoproterenol concentrations were significantly higher in COPD patients, thermogenesis related to isoproterenol concentration was significantly reduced in this group (P < 0.05). In conclusion, beta-adrenoceptor-mediated lipolysis and thermogenesis are impaired in COPD patients. This may play a role in the development or maintenance of their relatively increased fat mass.

Adrenergic beta-Agonists↗
PubMed2001

Weight reduction and the impaired plasma-derived free fatty acid oxidation in type 2 diabetic subjects.

In a previous study the oxidation of plasma free fatty acids (FFA) under baseline conditions and during exercise was lower in type 2 diabetic subjects compared with weight-matched controls. The present study intended to investigate the effect of weight reduction (very low calorie diet) on plasma FFA oxidation in seven type 2 diabetic male subjects (body fat, 37.4 +/- 1.2%; age, 51.3 +/- 3.4 yr; plasma glucose, 7.45 +/- 0.48 mmol/L). Subjects underwent a 10-week diet period. Body composition and substrate utilization during rest and during bicycle exercise (50% of maximum aerobic capacity) were determined before and after the diet (during weight-stable conditions). FFA metabolism was studied by means of the tracer [U-(13)C]palmitate. Rates of oxidation of plasma FFA were corrected with an acetate recovery factor. Additionally, activities of mitochondrial enzymes and cytosolic fatty acid-binding protein were determined in biopsies from the vastus lateralis muscle before and after the diet. The very low calorie diet resulted in a weight loss of 15.3 kg (110.8 +/- 7.4 vs. 95.5 +/- 5.8 kg; P < 0.01). The basal rates of appearance and disappearance of FFA decreased as a result of diet. The rates of appearance and disappearance of FFA during exercise were not different before and after diet. The oxidation of plasma-derived fatty acids tended to decrease after diet during baseline conditions (P = 0.10), whereas the plasma FFA oxidation during exercise was not different before and after the diet (14.1 +/- 1.9 vs. 14.8 +/- 1.8 micromol/kg fat-free mass.min). Skeletal muscle cytosolic fatty acid-binding protein and the activities of muscle oxidative enzymes did not significantly change as a result of weight loss. In conclusion, considerable weight reduction did not significantly improve plasma-derived FFA oxidation under baseline conditions and during exercise, suggesting that this impairment reflects a primary defect leading to the development of type 2 diabetes mellitus rather than resulting from the type 2 diabetic state.

Arteries↗
PubMed2001

Plasma free Fatty Acid uptake and oxidation are already diminished in subjects at high risk for developing type 2 diabetes.

The objective of this study was to investigate to what extent disturbances in fatty acid metabolism found in type 2 diabetes are already present in subjects at high risk for developing diabetes (i.e., impaired glucose tolerance [IGT]). Components of fatty acid metabolism were measured in male subjects with IGT during postabsorptive conditions and during 60 min of exercise (50% VO(2max)) with the use of the stable isotope tracer [U-(13)C]palmitate in combination with indirect calorimetry, and those values were compared with previously published findings in male type 2 diabetic and male obese subjects. No differences were found between groups in energy expenditure and in total fat and carbohydrate oxidation. Rate of appearance and rate of disappearance of plasma free fatty acid (FFA) were lower in subjects with IGT and type 2 diabetes compared with obese subjects (P < 0.05). Plasma FFA oxidation was lower in subjects with IGT and type 2 diabetes compared with obese subjects at rest and tended to be lower during exercise (rest: 3.7 +/- 0.3, 4.4 +/- 0.6, and 6.9 +/- 1.0 micromol. kg fat-free mass [FFM](-1). min(-1), P < 0.01; exercise: 15.0 +/- 1.7, 14.1 +/- 1.9, and 19.6 +/- 1.5 micromol. kg FFM(-1). min(-1) for IGT, type 2 diabetic, and obese subjects, respectively, P = 0.07). Triglyceride-derived fatty acid oxidation, however, was elevated in subjects with IGT and type 2 diabetes during exercise (3.6 +/- 1.4, 1.4 +/- 1.4, and -4.0 +/- 2.0 micromol. kg FFM(-1). min(-1) for IGT, type 2 diabetic, and obese subjects, respectively; P < 0.05). These data demonstrate that male subjects with a prediabetic condition (IGT) have the same defects in fatty acid utilization as subjects with type 2 diabetes, suggesting that these disturbances may play an important role in the progression from IGT to type 2 diabetes.

Adult↗
PubMed2001

Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes.

Recently, a role for uncoupling protein-3 (UCP3) in carbohydrate metabolism and in type 2 diabetes has been suggested. Mice overexpressing UCP3 in skeletal muscle showed reduced fasting plasma glucose levels, improved glucose tolerance after an oral glucose load, and reduced fasting plasma insulin levels. However, data regarding the expression of UCP3 in patients with type 2 diabetes is inconsistent, and so far, there have been no reports of UCP3 protein content. Here we compared, for the first time, the protein levels of UCP3 in vastus lateralis muscle in 14 male type 2 diabetic patients (age 49.8 +/- 2.1 years; BMI 27.2 +/- 1.2 kg/m(2); mean +/- SE) with 16 male control subjects (age 48.0 +/- 1.9 years; BMI 23.4 +/- 0.6 kg/m(2)). We found that UCP3 protein levels were twice as low in patients with type 2 diabetes compared with control subjects (117 +/- 16 vs. 58 +/- 12 AU; P = 0.007). There was no correlation between UCP3 content and BMI. In conclusion, UCP3 content is lower in type 2 diabetic patients compared with healthy control subjects. These results are consistent with a role for UCP3 in glucose homeostasis and suggest a role for UCP3 in type 2 diabetes.

Blood Glucose↗
PubMed2000

The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in Type II diabetic subjects.

AIMS/HYPOTHESIS: The aim of this study was to examine the effect of weight loss on UCP2/UCP3 mRNA expression and UCP3 protein content in subjects with Type II (non-insulin-dependent) diabetes mellitus. METHODS: We studied seven Type II diabetic subjects who followed a 10-week very low calorie diet. Expression of skeletal muscle UCP2 and UCP3 mRNA was measured using RT-competitive PCR and UCP3 protein content by western blotting, before and after the diet. Total and plasma fatty acid oxidation was measured using infusion of 13C labelled palmitate. RESULTS: Body weight decreased from 105.5 +/- 8.2 kg to 91.6 +/- 7.2 kg (p < 0.001), after 10 weeks of diet intervention. Expression of UCP2 and UCP3 mRNA were significantly reduced after 10 weeks of diet (p < 0.05) but UCP3 protein contents were not significantly altered. Notably, the change in UCP3L mRNA expression and UCP3 protein content after the very low calorie diet were negatively associated with changes in body weight (r = -0.97, p = 0.006 and r = -0.83, p = 0.043, respectively) and BMI (r = -0.99, p = 0.0007 and r = -0.9, p = 0.016, respectively). Furthermore, changes in UCP3L mRNA expression and UCP3 protein content induced by the diet were positively correlated with changes in cytosolic fatty acid-binding protein content (r = 0.93, p = 0.023 and r = 0.84, p = 0.039, respectively). No correlation between diet-induced changes in UCP3 protein and resting energy expenditure or plasma non-esterified fatty acid concentrations were found. CONCLUSION/INTERPRETATION: The negative correlation between the change in UCP3 protein content after weight loss and the change in BMI, suggests that the decrease in UCP3 during weight loss could prevent further weight loss. The finding that the change in UCP3 protein content correlates with the change in skeletal muscle fatty acid-binding protein content, suggests a role for UCPs in the handling of lipids as a fuel.

Antibody Specificity↗
PubMed2000

In vivo beta3-adrenergic stimulation of human thermogenesis and lipid use.

OBJECTIVE: To investigate the role of the human beta3-adrenergic receptor in in vivo isoproterenol (INN, isoprenaline)-induced thermogenesis and lipid use. METHODS: Eight male volunteers participated in two studies. In the first study subjects received oral dosages of 2.5, 7.5, 15, and 40 mg nadolol or propranolol (both beta1- and beta2-adrenergic receptor antagonists) at random, after which isoproterenol (beta1-, beta2-, and beta3-adrenergic receptor agonist) was infused in an individually determined dosage (range, 19 to 35 ng/kg x min) that increased energy expenditure by 25% without pretreatment. In the second study, 50, 100, and 200 ng/kg x min isoproterenol or saline solution were infused after pretreatment with 80 mg nadolol. In both studies energy expenditure and respiratory exchange ratio were measured by indirect calorimetry and, at the end of each infusion period, blood samples were taken and tremor score (only first study), heart rate, and blood pressure were measured. RESULTS: In the first study, nadolol or propranolol in doses < or =40 mg could not fully block beta1-adrenergic receptor-mediated increases in heart rate and systolic blood pressure. Propranolol in doses < or =7.5 mg could not fully block the beta2-adrenergic receptor-mediated increase in tremor score during isoproterenol infusion. The increases found in thermogenesis and lipid use could therefore be explained by concomitant beta1- and beta2-adrenergic stimulation. In the second study, isoproterenol infusion induced a significant increase in heart rate, but no increases in thermogenesis and lipid use were found compared with infusion of saline solution. CONCLUSION: No evidence could be found for a beta3-adrenergic receptor-mediated increase in human thermogenesis and lipid use during isoproterenol infusion after pretreatment with nadolol or propranolol.

Adrenergic beta-Agonists↗
PubMed2000

Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle.

In this study, we investigated the hypothesis that impairments in forearm skeletal muscle free fatty acid (FFA) metabolism are present in patients with type 2 diabetes both in the overnight fasted state and during beta-adrenergic stimulation. Eight obese subjects with type 2 diabetes and eight nonobese controls (Con) were studied using the forearm balance technique and indirect calorimetry during infusion of the stable isotope tracer [U-(13)C]palmitate after an overnight fast and during infusion of the nonselective beta-agonist isoprenaline (Iso, 20 ng. kg lean body mass(-1) x min(-1)). Additionally, activities of mitochondrial enzymes and of cytoplasmatic fatty acid-binding protein (FABP) were determined in biopsies from the vastus lateralis muscle. Both during fasting and Iso infusion, the tracer balance data showed that forearm muscle FFA uptake (Con vs. type 2: fast 449+/-69 vs. 258 +/-42 and Iso 715+/-129 vs. 398+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05) and FFA release were lower in type 2 diabetes compared with Con. Also, the oxidation of plasma FFA by skeletal muscle was blunted during Iso infusion in type 2 diabetes (Con vs. type 2: Iso 446 +/- 274 vs. 16+/-70 nmol. 100 ml tissue(-1) x min(-1), P<0.05). The net forearm glycerol release was increased in type 2 diabetic subjects (P< 0.05), which points to an increased forearm lipolysis. Additionally, skeletal muscle cytoplasmatic FABP content and the activity of muscle oxidative enzymes were lowered in type 2 diabetes. We conclude that the uptake and oxidation of plasma FFA are impaired in the forearm muscles of type 2 diabetic subjects in the overnight fasted state with and without Iso stimulation.

Acetates↗
PubMed2000

Impaired oxidation of plasma-derived fatty acids in type 2 diabetic subjects during moderate-intensity exercise.

The present study was intended to investigate the different components of fatty acid utilization during a 60-min period of moderate-intensity cycling exercise (50% of VO2max) in eight male type 2 diabetic subjects (aged 52.6 +/- 3.1 years, body fat 35.8 +/- 1.3%) and eight male obese control subjects (aged 45.1 +/- 1.4 years, body fat 34.2 +/- 1.3%) matched for age, body composition, and maximal aerobic capacity. To quantitate the different components of fatty acid metabolism, an isotope infusion of [U-13C]-palmitate was used in combination with indirect calorimetry. In separate experiments, the 13C label recovery in expired air was determined during infusion of [1,2-13C]-acetate (acetate recovery factor). There were no differences in energy expenditure or carbohydrate and total fat oxidation between the groups. The rate of appearance (Ra) of free fatty acid (FFA) (P < 0.05) and the exercise-induced increase in Ra of FFA were significantly lower (P < 0.05) in type 2 diabetic subjects compared with control subjects (baseline vs. exercise [40-60 min]; type 2 diabetes 11.9 +/- 0.9 vs. 19.6 +/- 2.2 micromol x kg(-1) fat-free mass [FFM] x min(-1) and control 15.8 +/- 1.8 vs. 28.6 +/- 2.1 micromol x kg(-1) FFM x min(-1)). The oxidation of plasma-derived fatty acids was significantly lower in type 2 diabetic subjects during both conditions (P < 0.05, baseline vs. exercise [40-60 min]; type 2 diabetes 4.2 +/- 0.5 vs. 14.1 +/- 1.9 micromol x kg(-1) FFM x min(-1) and control 6.2 +/- 0.6 vs. 20.4 +/- 1.9 micromol x kg(-1) FFM x min(-1)), whereas the oxidation of triglyceride-derived fatty acids was higher (P < 0.05). It is hypothesized that these impairments in fatty acid utilization may play a role in the etiology of skeletal muscle and hepatic insulin resistance.

Arteries↗
PubMed2000

Adrenergically stimulated fat utilization and ageing.

Ageing is associated with a diminished ability to use fat as a fuel during exercise. Also, middle-aged subjects have a blunted ability to mobilize fatty acids and to increase skeletal muscle fatty acid uptake and oxidation during intravenous beta-adrenergic stimulation, indicating that the sympathetic nervous system may play a role in the disturbed fat utilization. The blunted lipolytic response may be related to disturbances at the receptor level, eg a diminished number or agonist affinity of beta-adrenoceptors, or at the postreceptor level, eg a diminished activity of the hormone-sensitive lipase complex. As the rates of fatty acid availability are not limiting during exercise or beta-adrenergic stimulation in the elderly, the lowered skeletal muscle fat oxidation is probably related to an age-related decline in the capacity of skeletal muscle to oxidize fatty acids. Factors responsible for this decline may be a diminished content of oxidative enzymes, an increased glycolytic flux inhibiting fatty acid transport into the mitochondria, or a diminished (possibly beta-adrenergically-mediated) activation of fatty acid transport. It remains to be determined to what extent disturbances of fat metabolism may be related to the ageing process per se or whether they are secondary to age-related changes in body fat distribution and level of physical activity. Nevertheless, the impairments in sympathetically mediated lipolysis and fat oxidation may be of importance in the age-related increase in adiposity and insulin resistance and may thus be one of the links between ageing and increased prevalence of chronic diseases, such as obesity, type 2 diabetes mellitus, and cardiovascular disease.

Aging↗
PubMed2000

Determinants of the acetate recovery factor: implications for estimation of [13C]substrate oxidation.

When using (13)C or (14)C tracers to study substrate metabolism, an acetate correction factor should be applied to correct for loss of label in the exchange pathways of the tricarboxylic acid cycle. We have shown recently that the [(13)C]acetate recovery factor has a high inter-individual variability and should therefore be determined in every subject. In the present study we examined the factors that might explain some of the variability between subjects in acetate recovery factor. Data were pooled from four different studies with identical protocols, in which the acetate recovery factor was measured, prior to an intervention, to correct plasma fatty acid oxidation rates. Acetate recovery was measured after 2 h of [1, 2-(13)C]acetate infusion at rest followed by 1 h of cycling exercise at 40-50% of maximal oxygen uptake. Inter-individual variance in acetate recovery was 12.0% at rest and 16.1% during exercise. Stepwise regression revealed that, at rest, 37.1% of the acetate recovery could be accounted for by basal metabolic rate adjusted for fat-free mass, percentage body fat and respiratory quotient (RQ). During exercise, 69.1% of the variance in acetate recovery could be accounted for by energy expenditure adjusted for fat-free mass, % body fat and RQ. In conclusion, we show that the acetate recovery factor has a high inter-individual variability, both at rest and during exercise, which can partly be accounted for by metabolic rate, RQ and % body fat. These data indicate that the acetate recovery factor needs to be determined in every subject, under similar conditions as used for the tracer-derived determination of substrate oxidation. Failure to do this might result in large under- or over-estimation of plasma substrate oxidation, and hence to artificial differences between groups.

Acetic Acid↗
PubMed1999

Substrate utilization and thermogenic responses to beta-adrenergic stimulation in obese subjects with NIDDM.

OBJECTIVE: This study intended to investigate disturbances in beta-adrenergically-mediated substrate utilization and thermogenesis in obese subjects with mild non insulin-dependent diabetes mellitus (NIDDM). DESIGN: Following a baseline period of 30 min, the beta-agonist isoproterenol (ISO) was administered in increasing doses of 6, 12, and 24 ng/kgFFM x min, each dose for 30 min. SUBJECTS: Nine healthy lean males (CON, 50.6+/-2.4 y, % body fat: 16.0+/-1.8) and 10 obese subjects with NIDDM (51.8+/-2.4 y, % body fat 34.1+/-1.9). RESULTS: Basal non esterified fatty acid concentrations (NEFA) and basal fat oxidation (absolute or expressed per unit fat free mass, FFM) were significantly higher in NIDDM as compared to CON, whereas basal carbohydrate (CHO) oxidation was significantly lower. The ISO-induced increase in NEFA-concentrations was blunted in NIDDM (delta at 24 ng/kgFFM x min: CON: 717+/-59 micromol/l vs NIDDM: 358+/-97 micromol/l, P< 0.01). The non-protein respiratory exchange ratio (RER) did not change in NIDDM and significantly decreased in CON during ISO-infusion (P < 0.05), reflecting the tendency towards a blunted increase in fat oxidation in NIDDM (delta fat ox at 24 ng; CON: 0.025+/-0.005 g/min vs NIDDM 0.016+/-0.007 g/min). The ISO-induced thermogenic response was comparable in NIDDM and CON (at 24 ng %increase above baseline: CON: 16.8+/-2.2% vs NIDDM: 14.7+/-0.9%). At all time points, there were no significant differences in circulating ISO and noradrenaline concentrations. Basal adrenaline (A) concentrations and A concentrations during ISO-infusion were significantly lower in NIDDM (basal A; CON: 64+/-15 pg/ml vs NIDDM: 25+/-2 pg/ml, P < 0.001). CONCLUSION: There appear to be deviations in beta-adrenoceptor mediated fat utilization and adrenal medulla function in obesity-associated NIDDM. The impairments in sympathetically mediated fat utilization have previously been observed in 'simple' obese subjects, indicating that these disturbances are confined to the obese state per se.

Adrenergic beta-Agonists↗
PubMed1999

Microdialysis assessment of local adipose tissue lipolysis during beta-adrenergic stimulation in upper-body-obese subjects with type II diabetes.

The present study was designed to investigate indicators of abdominal adipose tissue lipolysis (microdialysis), and subcutaneous adipose tissue blood flow and whole-body lipolysis, in obesity-associated type II diabetes during overnight-fasted conditions (baseline) and during intravenous infusion of the non-selective beta-agonist isoprenaline. Basal subcutaneous adipose tissue blood flow and isoprenaline-induced increases in adipose tissue blood flow were not significantly different between subjects with type II diabetes and non-obese, non-diabetic controls. Adipose tissue interstitial glycerol concentrations were significantly higher in subjects with type II diabetes compared with controls (P<0. 01), and during isoprenaline infusion there was a decrease in interstitial glycerol in both groups (P<0.001). Arterial glycerol concentrations were higher in subjects with type II diabetes compared with controls (P<0.05), whereas the increases in arterial glycerol concentration in response to isoprenaline infusion were of a similar magnitude in the two groups. Estimated subcutaneous adipose tissue glycerol release was not significantly different between the groups (controls and subjects with type II diabetes: baseline, -129+/-32 and -97+/-72 micromol.min(-1).100 g(-1) adipose tissue respectively; isoprenaline, -231+/-76 and -286+/-98 micromol. min(-1).100 g(-1) respectively). Values for fat oxidation were not significantly different between groups, whereas the isoprenaline-induced increase in fat oxidation tended to be less pronounced in subjects with type II diabetes compared with controls (0.022+/-0.008 and 0.038+/-0.003 g/min respectively; P=0.058). Thus estimated basal subcutaneous adipose tissue glycerol release, expressed per unit of fat mass, is not different in controls and in subjects with type II diabetes. Additionally, the isoprenaline-induced increases in indicators of local abdominal subcutaneous adipose tissue, systemic lipolysis and abdominal adipose tissue blood flow responses were comparable in obese subjects with type II diabetes and in controls. The last two findings contrast with previous data from obese subjects, indicating that the regulation of lipolysis may differ in obesity and obesity-associated type II diabetes.

Adipose Tissue↗
PubMed1999

Beta-adrenergically stimulated fat oxidation is diminished in middle-aged compared to young subjects.

The effect of aging on beta-adrenergically mediated substrate utilization was investigated in nine young (25.2 +/- 1.7 yr old) and eight older males (52.9 +/- 2.1 yr old), matched for body weight and body composition. In a first experiment, the nonselective beta-agonist isoprenaline (ISO) was infused in increasing standardized doses, and during each infusion period energy expenditure and substrate utilization were determined by indirect calorimetry. In a second experiment, forearm skeletal muscle metabolism was studied during a standardized infusion dose of ISO (19 ng/kg fat-free mass x min). During beta-adrenergic stimulation there was an increased carbohydrate oxidation (at an ISO infusion dose of 24 ng/kg fat-free mass x min, 31% vs. 21% of total energy expenditure; P < 0.05) and a decreased fat oxidation (51 vs. 62 of total energy expenditure; P < 0.05) in older compared to young subjects. Skeletal muscle lactate release significantly increased in the older subjects (from -175 +/- 32 to -366 +/- 66 nmol/100 mL forearm tissue x min), whereas there was no change in young subjects (from -32 +/- 21 to 23 +/- 57 nmol/100 mL forearm tissue x min; interaction group x ISO, P < 0.01). Additionally, there was a tendency toward a blunted ISO-induced increase in nonesterified fatty acid uptake in the older subjects (interaction group x ISO, P = 0.062). Thus, middle-aged subjects have a blunted ability to oxidize fat during beta-adrenergic stimulation compared to young subjects. This diminished fat oxidation may be an important etiological factor in the age-related increase in body fatness and obesity by favoring fat storage above oxidation.

Adrenergic beta-Agonists↗
PubMed1998

Effect of aging on beta-adrenergically mediated thermogenesis in men.

The age-dependent alterations in beta-adrenergically mediated thermogenesis were investigated in 11 young (mean +/- SE age: 21.9 +/- 0.5 yr) and 9 older (52.9 +/- 2.1 yr) men during intravenous infusion of the nonselective beta-agonist isoprenaline (Iso). The older men had higher basal plasma norepinephrine (327.7 +/- 35.8 vs. 159.0 +/- 18.2 pg/ml, P < 0.001) and epinephrine (75.1 +/- 18.1 vs. 29.1 +/- 5.3 pg/ml, P < 0.05) concentrations than the young. The beta-adrenergically mediated thermogenesis was diminished in the older men, as reflected by the significantly higher plasma Iso concentration needed to increase resting energy expenditure by 15% (236.1 +/- 51.0 vs. 107.6 +/- 11.4 pg/ml, P < 0.05). Additionally, both dose (39.4 +/- 6.6 vs. 19.1 +/- 1.5 ng . kg fat-free mass-1 . min-1, P < 0.01) and plasma concentration (332.2 +/- 59.1 vs. 119.3 +/- 14.0 pg/ml, P < 0.01) of Iso needed to increase resting heart rate by 25 beats/min were higher in older than in younger subjects, suggesting that the age-related decline in beta-adrenergic sensitivity is a generalized defect not related to a specific tissue or response. In conclusion, aging is associated with a diminished beta-adrenergically mediated thermogenesis. This blunted thermogenic response may contribute to a positive energy balance and thus promote increased fat storage and obesity.

Adipose Tissue↗
PubMed1996

Postprandial thermogenesis and substrate utilization after ingestion of different dietary carbohydrates.

Whole-body thermogenesis, substrate utilization (open-circuit ventilated-hood system), and exogenous carbohydrate oxidation were evaluated in 10 healthy lean male volunteers (aged 27.8 +/- 2.5 years) for 6 hours after oral ingestion of 75 g naturally enriched fructose, glucose (both derived from corn starch), cane sugar, and a good digestible corn starch (all mixed with 400 mL water). The integrated areas under the glucose and insulin response curves above baseline were highest with glucose and starch, intermediate with sucrose, and lowest with fructose, whereas there were no significant differences in the integrated nonesterified fatty acid (NEFA) response between carbohydrates. The total increment in energy expenditure (EE) above baseline was similar with fructose (130 +/- 24 kJ/6 h) and sucrose (141 +/- 17 kJ/6 h), was higher with sucrose as compared with starch (108 +/- 24 kJ/6 h, P < .05) and glucose (94 +/- 20 kJ/6 h, P < .05), and tended to be higher with fructose as compared with glucose (P = .059). Both the increment in total carbohydrate oxidation (P < .05) and the increment in exogenous carbohydrate oxidation (P < .01) were significantly higher with fructose and sucrose compared with glucose and starch. The initial inhibition of lipid oxidation was higher with sucrose and fructose than with glucose and starch, whereas the integrated decrement in lipid oxidation over 6 hours was only higher with fructose compared with glucose and starch (P < .05). In conclusion, thermogenesis and substrate utilization vary considerably after ingestion of different types of carbohydrate in young lean males, indicating that the carbohydrate composition of the diet may have important consequences for energy and macronutrient balance.

Adult↗
PubMed1996

Agonist and antagonist properties of beta 3-adrenoceptors in human omental and mouse 3T3-L1 adipocytes.

The pharmacological properties of the native human beta 3-adrenoceptor are poorly defined. In the present study, the agonist and antagonist properties of beta 3-adrenoceptors in human omental and mouse 3T3-L1 adipocytes were compared by measuring lipolysis in the absence or presence of adrenoceptor blockers. Methodological experiments revealed that all three beta-adrenoceptors were functionally expressed in both types of adipocytes. This makes the human and the mouse cells directly comparable in pharmacological studies. CGP 12177 was a selective partial beta 3-adrenoceptor agonist in both cell types with a pD(2) of about 7.5. The order of potency of classical non-selective adrenoceptor agonists, when determined during blockade of beta 1-, beta 2- and alpha 2-adrenoceptors, was isoprenaline>noradrenaline>adrenaline in both human and 3T3-L1 adipocytes. This is different from the order of potency of the same agonists at the beta 1- or beta 2-adrenoceptors. The sensitivity of the beta 3-adrenoceptor to these catecholamines, expressed as pD(2) values, were virtually identical in both adipocyte types. Isoprenaline, noradrenaline, and adrenaline were almost full agonists in both cell types (intrinsic activity from 74% or 95%) during combined beta 1, beta 2- and alpha 2-adrenoceptor blockade. Antagonist potencies (expressed as pA(2) and using CGP 12177 as agonist) at the alpha 3-adrenoceptor were similar in both adipocyte types: bupranolol>propranolol>metoprolol. The corresponding pA(2) values for bupranolol, propanolol and metoprolol were about 7, 6 and 5, respectively in both species. In conclusion, the pharmacological properties of classical catecholamines, beta-adrenoceptor blockers and CGP 12177 are almost identical at the beta 3-adrenoceptors of human omental adipocytes and 3T3-L1 adipocytes.

Adipose Tissue↗
PubMed1995

Beta-adrenergically mediated thermogenic and heart rate responses: effect of obesity and weight loss.

beta-Adrenergically mediated thermogenic and heart rate (HR) responses, as assessed by stepwise intravenous infusion of the beta-agonist isoprenaline (ISO), were evaluated by partial regression analysis in a group of men with a wide range of body fat (n = 30) and in a subgroup of 16 obese men after weight loss. beta-Adrenergically mediated thermogenesis (open-circuit ventilated-hood system) was blunted in obese subjects, as reflected by a significant positive correlation between percent body fat (hydrostatic weighing) and the plasma ISO concentration needed to increase resting energy expenditure (EE) by 15% (P < .001). The magnitude of the beta-adrenergically mediated HR response was (negatively) associated with the basal plasma norepinephrine (NE) concentration (P < .001). Weight reduction resulted in a significant increase in thermogenic and HR responses in obese subjects. Furthermore, the increase in thermogenic response as a result of weight loss was negatively related to the magnitude of thermogenic response (P < .01) and positively related to the initial percent body fat (P < .05). The increase in HR response as a result of weight loss was positively related to the decrease in basal NE (P < .01) and the change in percent body fat (P < .05). In conclusion, the degree of adiposity was shown to be negatively related to the magnitude of beta-adrenergically mediated thermogenesis, whereas the HR response was merely related to basal NE. Since weight loss resulted in a significant increase in the thermogenic response, the blunted beta-adrenergically mediated thermogenesis does not seem to be a primary factor contributing to the development of obesity.

Adult↗