Biomedical subjects

M A van Baak

Publications and source records attributed to M A van Baak.

At least 19 recordsLinked to original sources

PubMed2006

Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation.

BACKGROUND AND AIMS: Obesity is associated with a blunted beta-adrenoceptor-mediated lipolysis and fat oxidation. We investigated whether polymorphisms in codon 16, 27 and 164 of the beta (2)-adrenoceptor gene (ADRB2) and exon 10 of the G protein beta (3)-subunit gene (GNB3) are associated with alterations in in vivo lipolysis and fat oxidation. DESIGN AND METHODS: Sixty-five male and 43 female overweight and obese subjects (body mass index (BMI) range: 26.1-48.4 kg/m(2)) were included. Energy expenditure (EE), respiratory quotient (RQ), circulating free fatty acid (FFA) and glycerol levels were determined after stepwise infusion of increasing doses of the non-selective beta-agonist isoprenaline (ISO). RESULTS: In women, the Arg16 allele of the ADRB2 gene was associated with a blunted increase in circulating FFA, glycerol and a decreased fat oxidation during ISO stimulation. In men, the Arg16 allele was significantly associated with a blunted increase in FFA but not in glycerol or fat oxidation. CONCLUSION: These results suggest that genetic variation in the ADRB2 gene is associated with disturbances in in vivo beta-adrenoceptor-mediated lipolysis and fat oxidation during beta-adrenergic stimulation in overweight and obese subjects; these effects are influenced by gene-gender interactions.

Adipose Tissue↗

PubMed2006

Effect of short-term ACE inhibitor treatment on peripheral insulin sensitivity in obese insulin-resistant subjects.

AIMS/HYPOTHESIS: This study was designed to investigate the effect of short-term ACE inhibitor treatment on insulin sensitivity and to examine possible underlying metabolic and haemodynamic effects in obese insulin-resistant subjects. METHODS: A randomised, double-blind placebo-controlled trial was performed in 18 obese insulin-resistant men (age, 53 +/- 2 years; BMI, 32.6 +/- 0.8 kg/m(2); homeostasis model assessment of insulin resistance, 5.6 +/- 0.5; systolic blood pressure [SBP], 140.8 +/- 3.2; diastolic blood pressure [DBP], 88.8 +/- 1.6 mmHg), who were free of any medication. The aim was to examine the effects of 2 weeks of ACE inhibitor treatment (ramipril, 5 mg/day) on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and intramuscular triacylglycerol (IMTG) content. RESULTS: Ramipril treatment decreased ACE activity compared with placebo (-22.0 +/- 1.7 vs 0.2 +/- 1.1 U/l, respectively, p < 0.001), resulting in a significantly reduced blood pressure (SBP, -10.8 +/- 2.1 vs -2.7 +/- 2.0 mmHg, respectively, p = 0.01; DBP, -10.1 +/- 1.3 vs -4.2 +/- 2.1 mmHg, respectively, p = 0.03). Ramipril treatment had no effect on whole-body insulin-mediated glucose disposal (before: 17.9 +/- 2.0, after: 19.1 +/- 2.4 micromol kg body weight(-1) min(-1), p = 0.44), insulin-mediated glucose uptake across the forearm (before: 1.82 +/- 0.39, after: 1.92 +/- 0.29 micromol 100 ml forearm tissue(-1) min(-1), p = 0.81) and IMTG content (before: 45.4 +/- 18.8, after: 48.8 +/- 27.5 micromol/mg dry muscle, p = 0.92). Furthermore, the increase in carbohydrate oxidation (p < 0.001) and forearm blood flow (p < 0.01), and the decrease in fat oxidation (p < 0.001) during insulin stimulation were not significantly different between treatments. CONCLUSIONS/INTERPRETATION: Short-term ramipril treatment adequately reduced ACE activity and blood pressure, but had no significant effects on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and IMTG content in obese insulin-resistant subjects.

Angiotensin II↗

PubMed2006

Angiotensin II: a hormone that affects lipid metabolism in adipose tissue.

BACKGROUND: Alterations in adipose tissue lipolysis may contribute to the pathophysiology of obesity and insulin resistance. We examined the effects of angiotensin II (Ang II) on abdominal subcutaneous adipose tissue lipolysis in humans. METHODS AND RESULTS: First, adipocytes obtained from nine normal weight and seven obese subjects were stimulated with Ang II (10(-14)-10(-6) M). Glycerol concentration in the medium, used as an indicator of adipocyte lipolysis, was significantly reduced (approximately 20%) after Ang II stimulation in adipocytes from normal weight (P=0.04) and obese subjects (P<0.001). Based on these observations, adipocytes of seven additional obese subjects were stimulated with lower doses of Ang II (10(-17)-10(-6) M) in the presence and absence of Ang II type 1 (AT(1)) receptor blockade. Lipolysis was dose dependently inhibited by approximately 20 to 25% after Ang II stimulation (P=0.001). AT(1) receptor blockade completely abolished the Ang II-induced effects (P=0.35). CONCLUSION: Ang II directly inhibits abdominal subcutaneous adipocyte lipolysis in normal weight and obese subjects via the AT(1) receptor.

Adipocytes↗

PubMed2006

Angiotensin II: a major regulator of subcutaneous adipose tissue blood flow in humans.

We investigated the functional roles of circulating and locally produced angiotensin II (Ang II) in fasting and postprandial adipose tissue blood flow (ATBF) regulation and examined the interaction between Ang II and nitric oxide (NO) in ATBF regulation. Local effects of the pharmacological agents (or contralateral saline) on ATBF, measured with 133Xe wash-out, were assessed using the recently developed microinfusion technique. Fasting and postprandial (75 g glucose challenge) ATBF regulation was investigated in nine lean healthy subjects (age, 29 +/- 3 years; BMI, 23.4 +/- 0.7 kg m(-2)) using local Ang II stimulation, Ang II type 1 (AT1) receptor blockade, and angiotensin-converting enzyme (ACE) inhibition. Furthermore, NO synthase (NOS) blockade alone and in combination with AT1 receptor blockade was used to examine the interaction between Ang II and NO. Ang II induced a dose-dependent decrease in ATBF (10(-9)m: -16%, P = 0.04; 10(-7)m: -33%, P < 0.01; 10(-5)m: -53%P < 0.01). Fasting ATBF was not affected by ACE inhibition, but was increased by approximately 55% (P < 0.01) by AT(1) receptor blockade. NOS blockade induced a approximately 30% (P = 0.001) decrease in fasting ATBF. Combined AT1 receptor and NOS blockade increased ATBF by approximately 40% (P = 0.003). ACE inhibition and AT1 receptor blockade did not affect the postprandial increase in ATBF. We therefore conclude that circulating Ang II is a major regulator of fasting ATBF, and a major proportion of the Ang II-induced decrease in ATBF is NO independent. Locally produced Ang II does not appear to regulate ATBF. Ang II appears to have no major effect on the postprandial enhancement of ATBF.

Adipose Tissue↗

PubMed2005

Participation rates in worksite-based intervention studies: health promotion context as a crucial quality criterion.

Recently, a set of specific quality evaluation criteria for health promotion research has been proposed in this journal. One of the quality criteria identified is the 'health promotion context'. With this paper we would like to contribute to the dialogue by specifying the importance of this criterion on the basis of our on experience with worksite-based obesity prevention interventions. We advocate the reporting of participation rates among approached worksites in publications on worksite intervention effects. Such information will help to draw conclusions on the practical relevance of the shown effectiveness of the intervention. Health promotion practice is advised to adopt and disseminate evidence-based interventions, accompanied by a diffusion study with a minimal research burden for participants.

Health Promotion↗

PubMed2005

beta2-adrenergic receptor polymorphisms and salbutamol-stimulated energy expenditure.

The beta-adrenergic system is involved in the control of energy metabolism and expenditure. The beta2-adrenergic receptor (beta2-AR) gene shows polymorphisms that have been associated with obesity in several studies. In vitro and in vivo studies suggest differences in beta2-AR-mediated function between these polymorphisms. The aim of this study was to investigate the influence of genetic variation in codon 16 of the beta2-AR gene on energy metabolism in humans. Thirty-four subjects were recruited [Gly16Gly (n = 13), Gly16Arg (n = 16), or Arg16Arg (n = 5)]. The beta2-AR was stimulated with two doses of salbutamol (50 and 100 ng/kg fat-free mass per minute) after blockade of the beta1-adrenergic receptors with atenolol. Energy expenditure and plasma substrate and hormone concentrations were measured. The increase in energy expenditure (DeltaEE) was significantly different among groups in which the Arg16Arg group showed the lowest increase (P < 0.05 vs. Gly carriers). In a multiple regression model, variations in the increase in nonesterified fatty acid concentration during salbutamol infusion (partial r = 0.51) and the polymorphism contributed significantly to the variation in DeltaEE. Thirty-five percent of the variation in DeltaEE was explained by these two factors. We conclude that subjects with the Arg16Arg polymorphism of the beta2-AR gene have a reduced thermogenic response to beta2-adrenergic stimulation. Although this relatively small study needs confirmation, the findings support a role for this polymorphism in the development and maintenance of overweight and obesity.

Adult↗

PubMed2005

Influence of beta(2)-adrenoceptor gene polymorphisms on diet-induced thermogenesis.

The sympathetic nervous system is involved in the control of energy metabolism and expenditure. Diet-induced thermogenesis is mediated partly by the ss-adrenergic component of this system. The aim of the present study was to investigate the role of genetic variation in the beta(2)-adrenoceptor in diet-induced thermogenesis. Data from twenty-four subjects (fourteen men and ten women; BMI 26.7(sem 0.8) kg/m(2); age 45.2(sem1.4) years) with different polymorphisms of the beta(2)-adrenoceptor at codon 16 (Gly16Gly, Gly16Arg or Arg16Arg) were recruited for this study. Subjects were given a high-carbohydrate liquid meal, and the energy expenditure, respiratory exchange ratio, and plasma concentrations of NEFA, glycerol, glucose, insulin and catecholamines were measured before and over 4 h after the meal. The AUC of energy expenditure (diet-induced thermogenesis) was not significantly different between polymorphism groups, nor was the response of any of the other measured variables to the meal. In a multiple regression model, the only variable that explained a significant proportion (32 %) of the variation in diet-induced thermogenesis was the increase in plasma adrenaline in response to the meal (P<0.05). The beta(2)-adrenoceptor codon16 polymorphisms did not contribute significantly. In conclusion, an independent contribution of the codon 16 polymorphism of the beta(2)-adrenoceptor gene to the variation in thermogenic response to a high-carbohydrate meal could not be demonstrated. The interindividual variation in thermogenic response to the meal was correlated with variations in the plasma adrenaline response to the meal.

Adipose Tissue↗

PubMed2004

Inhaled salbutamol and endurance cycling performance in non-asthmatic athletes.

Beta(2)-adrenergic agonists are important therapeutic agents for the prevention and treatment of (exercise-induced) asthma in athletes, but may have ergogenic effects. In this study we investigated whether inhalation of a supra-therapeutic dose of 800 microg salbutamol before exercise affects endurance performance during a cycling trial in non-asthmatic athletes. In a double-blind, randomized cross-over study, 16 athletes performed two trials, where they had to perform a certain amount of work as fast as possible on a cycle ergometer, 30 minutes after inhalation of 800 micro g salbutamol or placebo. Peak expiratory flow (PEF), forced vital capacity (FVC), and forced expiratory volume in 1 second (FEV(1)) were measured before and after exercise and blood samples were obtained before and during exercise. Cycling performance time was 4010.2 +/- 327.7 s after placebo inhalation and 3927.6 +/- 231.3 s after inhalation salbutamol (p < 0.05). Although salbutamol inhalation increased plasma free fatty acids, glycerol and lactate concentrations and decreased plasma potassium concentrations at rest, no differences between placebo and salbutamol in these variables were found during exercise. PEF and FEV(1) were increased after salbutamol inhalation at rest compared with placebo, but the difference between placebo and salbutamol after exercise was no longer significant. Inhalation of a supratherapeutic dose of 800 micro g salbutamol improved endurance cycling performance by 1.9 +/- 1.8 % in non-asthmatic athletes, which indicates that this route of administration does not exclude the possibility of an ergogenic effect of beta(2)-adrenergic agents in athletes. The increase in performance was not explained by changes in plasma concentrations of free fatty acids, glycerol, lactate, and potassium during exercise or by changes in ventilatory parameters at rest and after exercise. Therefore, the mechanism of the increase in performance remains to be determined.

Administration, Inhalation↗

PubMed2004

Angiotensin II-induced effects on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects.

The present study was designed to investigate the effects of angiotensin II (Ang II) on adipose and skeletal muscle tissue blood flow and lipolysis in normal-weight and obese subjects using the microdialysis technique. Microdialysis probes were placed in the abdominal sc adipose tissue left and right from the umbilicus and in the gastrocnemius muscle of both legs in eight normal-weight and eight obese men. Probes were consecutively perfused with 1.0 nM Ang II, 1.0 microM Ang II, and 1.0 microM Ang II + 48 microM hydralazine or with Ringer solution (control). Ethanol and glycerol concentrations in the dialysate were measured as an indicator of local blood flow and lipolysis, respectively. Ang II caused an increase in ethanol outflow/inflow ratio, compared with baseline values both in adipose tissue (average of both groups, Ang 1.0 nM: 0.03 +/- 0.01, P = 0.02; Ang 1.0 microM: 0.05 +/- 0.01, P < 0.01) and muscle (average of both groups, Ang 1.0 nM: 0.02 +/- 0.01, P = 0.09; Ang 1.0 microM: 0.04 +/- 0.01, P = 0.01), indicating a decrease in local blood flow. These effects were not significantly different in obese and normal-weight subjects. The decrease in local blood flow was accompanied by unchanged interstitial glycerol concentrations in adipose tissue (except during the supraphysiological dose) and skeletal muscle, suggesting that Ang II inhibits lipolysis in both tissues. Thus, the present data suggest that Ang II decreases local blood flow in a dose-dependent manner and inhibits lipolysis both in adipose and skeletal muscle tissue. These effects were not significantly different in obese and normal-weight subjects in both tissues.

Adipose Tissue↗

PubMed2003

Possible involvement of the adipose tissue renin-angiotensin system in the pathophysiology of obesity and obesity-related disorders.

Angiotensin II (Ang II), acting on the AT1 and AT2 receptors in mammalian cells, is the vasoactive component of the renin-angiotensin system (RAS). Several components of the RAS have been demonstrated in different tissues, including adipose tissue. Although the effects of Ang II on metabolism have not been studied widely, it is intriguing to assume that components of the RAS produced by adipocytes may play an autocrine, a paracrine and/or an endocrine role in the pathophysiology of obesity and provide a potential pathway through which obesity leads to hypertension and type 2 diabetes mellitus. In the first part of this review, we will describe the production of Ang II, the different receptors through which Ang II exerts its effects and summarize the concomitant intracellular signalling cascades. Thereafter, potential Ang II-induced mechanisms, which may be associated with obesity and obesity-related disorders, will be considered. Finally, we will focus on the different pharmaceutical agents that interfere with the RAS and highlight the possible implications of these drugs in the treatment of obesity-related disorders.

Adipose Tissue↗

PubMed2003

How much physical activity is enough to prevent unhealthy weight gain? Outcome of the IASO 1st Stock Conference and consensus statement.

A consensus meeting was held in Bangkok, 21-23 May 2002, where experts and young scientists in the field of physical activity, energy expenditure and body-weight regulation discussed the different aspects of physical activity in relation to the emerging problem of obesity worldwide. The following consensus statement was accepted unanimously. 'The current physical activity guideline for adults of 30 minutes of moderate intensity activity daily, preferably all days of the week, is of importance for limiting health risks for a number of chronic diseases including coronary heart disease and diabetes. However for preventing weight gain or regain this guideline is likely to be insufficient for many individuals in the current environment. There is compelling evidence that prevention of weight regain in formerly obese individuals requires 60-90 minutes of moderate intensity activity or lesser amounts of vigorous intensity activity. Although definitive data are lacking, it seems likely that moderate intensity activity of approximately 45 to 60 minutes per day, or 1.7 PAL (Physical Activity Level) is required to prevent the transition to overweight or obesity. For children, even more activity time is recommended. A good approach for many individuals to obtain the recommended level of physical activity is to reduce sedentary behaviour by incorporating more incidental and leisure-time activity into the daily routine. Political action is imperative to effect physical and social environmental changes to enable and encourage physical activity. Settings in which these environmental changes can be implemented include the urban and transportation infrastructure, schools, and workplaces.'

Adult↗

PubMed2002

Genetic factors as predictors of weight gain in young adult Dutch men and women.

OBJECTIVE: To investigate the association between DNA polymorphisms in several candidate genes for obesity and weight gain. Polymorphisms in these genes may contribute to weight gain through effects on energy intake, energy expenditure or adipogenesis. DESIGN AND METHODS: From two large cohorts in The Netherlands (total 17,500 adult men and women), we compared 286 subjects aged 20-40 y who gained an average of 12.8 kg (range 5.5-47 kg) during a mean follow-up of 6.8 y with 296 subjects who remained relatively constant over the same period with respect to occurrence of several polymorphisms in candidate genes of obesity and some lifestyle factors. Subjects who were dieting, were high alcohol consumers, were pregnant, changed their smoking status recently, or those who suffered from serious illnesses were excluded. Polymorphisms were determined in the LEPR-gene (LEPR Lys109Arg, LEPR Gln223Arg, LEPR Lys656Asn), in the UCP1 gene (A-G mutation at position-3826 5' region), in the UCP2 gene (Ala55Val, 45 bp Ins/Del), in the PPARG2 gene (Pro12Ala) and in the ADRB2 gene (Gly16Arg and Gln27Glu). RESULTS: With the exception of the Gly16Arg polymorphism in the ADRB2 gene in men (P = 0.04) and women (P = 0.05), and the Lys109Arg polymorphism in the LEPR gene in women, no statistically significant differences in the genotype and allele frequencies were observed between weight gainers and non-weight gainers. Weight gainers differed in some aspects of dietary habits and physical activity patterns: weight gainers consumed relatively more savory snacks and were less active during leisure time compared with non-weight gainers. CONCLUSION: Only variations in the ADRB2 gene and LEPR gene, may contribute to susceptibility to weight gain. None of the other studied genetic markers were clearly associated with weight gain. Further research is necessary to establish the role of lifestyle factors, or interactions between genes or between genes and lifestyle factors on weight gain with age.

Adult↗

PubMed2001

The effect of low-intensity exercise training on fat metabolism of obese women.

OBJECTIVE: Previous studies have shown that fat metabolism is different in upper body (UB) and lower body (LB) obese women. The present study investigated whether the effect of low-intensity exercise training on fat metabolism is different in UB and LB obese premenopausal women. RESEARCH METHODS AND PROCEDURES: Twenty-one healthy, premenopausal women with either LB obesity (waist-to-hip ratio of < or =0.79; n = 8) or UB obesity (waist-to-hip ratio of > or =0.85; n = 13) participated in the present study. The UB obese women were matched and randomly divided in an exercise training group (UB) and a nonexercising control group (UB-C). Subjects in the UB and LB groups participated in a low-intensity exercise training program (40% VO2max) three times per week for 12 weeks. Before and after the intervention, measurements of fat metabolism at rest and during exercise, body composition, and maximal aerobic capacity were performed. RESULTS: Exercise training did not change the respiratory exchange ratio at rest in the UB and LB groups. During exercise, relative fat oxidation increased in the UB group by 19% (p < 0.05), whereas no change in the LB and UB-C groups was found. Plasma free fatty acid oxidation did not change by exercise training, and nonplasma fatty acid oxidation tended to increase in the UB group compared with the UB-C group (p = 0.08). DISCUSSION: Low-intensity exercise training increased the contribution of fat oxidation to total energy expenditure during exercise but not at rest in UB obese women. Exercise training had no significant effect on fat metabolism in the LB obese women.

Adipose Tissue↗

PubMed2001

The effect of exercise training on beta-adrenergic stimulation of fat metabolism in obese men.

OBJECTIVE: To investigate the in vivo effect of exercise training at high and low intensity on beta-adrenergic stimulated fat metabolism in obese men at rest. METHOD: Twenty-three obese, healthy subjects were randomly divided in a low-intensity exercise training program (40% VO(2max), n=7), a high-intensity exercise training program (70% VO(2max); n=8), or a non-exercising control group (n=8). The exercise training program lasted for 12 weeks with a training frequency of 3 times per week. Before and after the intervention body composition and maximal aerobic capacity were measured as well as fat metabolism at rest and during beta-adrenergic stimulation by isoprenaline. For comparison, six lean subjects served as a control group. They participated in a low-intensity exercise training program and underwent the same measurements as the obese subjects. RESULTS: Relative fat oxidation decreased significantly during infusion of an increasing dose of isoprenaline in the obese low-intensity and high-intensity exercise training groups as well as in the lean group (P<0.01). Exercise training failed to influence the effect of beta-adrenergic stimulation on relative fat oxidation in obese men at both intensities and in lean men. In addition, beta-adrenergic-mediated lipolysis did not seem to be different after low intensity exercise training in lean and obese men. Lipolysis might be increased after high-intensity exercise training in obese men. CONCLUSION: Low- and high-intensity exercise training in obese men failed to affect beta-adrenergic mediated relative fat oxidation in vivo. beta-Adrenergic-mediated lipolysis might be increased in obese men after HI exercise training only. The effect of low-intensity exercise training on beta-adrenergic-mediated fat metabolism was similar in lean and obese men. International Journal of Obesity (2001) 25, 16-23

Adrenergic beta-Agonists↗

PubMed2001

The effect of an increased free fatty acid concentration on thermogenesis and substrate oxidation in obese and lean men.

OBJECTIVE: To examine whether a certain increase in plasma free fatty acid (FFA) concentration leads to similar increases in lipid oxidation and energy expenditure in obese and lean men. DESIGN: The study protocol consisted of a 30 min baseline period after which subjects received an i.v. bolus of 1000 IE heparin. Then consecutive infusions of 4.9, 9.8 and 19.6 microl/kg fat-free mass (FFM).min of a lipid heparin mixture were started, each infusion for 30 min. SUBJECTS: Eleven obese and 13 lean men with a mean body mass index (BMI) of 34.2+/-1.0 (+/-s.e.m.) and 23.9+/-0.5 kg/m(2) and age 46.0+/-1.0 and 42.6+/-1.5 y, respectively. MEASUREMENTS: Energy expenditure, respiratory exchange ratio (RER) and carbohydrate and lipid oxidation were continuously measured by indirect calorimetry. At the end of each infusion period, a blood sample was taken for FFA, glycerol, insulin, beta-hydroxybutyrate, noradrenaline and adrenaline determination. RESULTS: At baseline, plasma FFA levels were comparable in both groups. Lipid heparin infusion increased plasma FFA concentration by 301+/-47 micromol/l and 332+/-27 micromol/l in obese and lean men. Energy expenditure increased similarly in obese and lean men (0.34+/-0.08 vs 0.40+/-0.08 kJ/min, NS) during lipid heparin infusion, whereas RER decreased similarly in both groups. Lipid oxidation rates were comparable at baseline and increased similarly in obese and lean men (19+/-5 vs 13+/-4 mg/min, NS). Baseline plasma insulin levels were higher in the obese, but did not change during lipid heparin infusion. Plasma beta-hydroxybutyrate concentrations were similar at baseline, but increased significantly less in the obese during lipid heparin infusion. Baseline noradrenaline and adrenaline concentrations did not differ significantly between groups. During lipid heparin infusion, plasma noradrenaline levels decreased significantly, but plasma adrenaline levels remained unchanged in both groups. CONCLUSION: A certain increase in plasma FFA concentration leads to similar increases in lipid oxidation and energy expenditure in obese and lean men. The accumulation of fat in obese subjects may therefore be more likely to be due to a defect in adipose tissue lipolysis than a defect in lipid oxidation. International Journal of Obesity (2001) 25, 33-38

Adult↗

PubMed2001

The peripheral sympathetic nervous system in human obesity.

The peripheral sympathetic nervous system is a key factor in the regulation of energy balance in humans. Differences in sympathetic nervous system activity may contribute to variations in 24 h energy expenditure between individuals. beta-Adrenoceptors play a more important role than alpha-adrenoceptors in this regulation. The involvement of both beta 1- and beta 2-adrenoceptor subtypes has been demonstrated, the role of the beta 3-adrenoceptor subtype is not yet clear. Normal or increased levels of sympathetic nervous system activity and reduced reactivity appear to be present in established obesity. Furthermore, the sensitivity for beta-adrenoceptor stimulation is impaired in obesity. The blunted reactivity and sensitivity may contribute to the maintenance of the obese state. There are data to suggest that they may also play a role in the aetiology of obesity, because the impairments often remain after weight reduction. Furthermore, a negative correlation between baseline sympathetic nervous system activity and weight gain during follow-up has been found in Pima Indians. Recently, genetic evidence about the involvement of adrenoceptors in obesity has become available. Although the results of association and linkage studies on polymorphisms in the beta 2-, beta 3- and alpha 2-adrenoceptor genes are inconsistent, the functional correlates of some of these polymorphisms (changes in agonist-promoted down-regulation, protein expression levels, lipolytic sensitivity, basal metabolic rate, sympathetic nervous system activity) suggest that they may be important in the aetiology of obesity.

Energy Metabolism↗

PubMed2001

Short-term effects of weight loss with or without low-intensity exercise training on fat metabolism in obese men.

BACKGROUND: Energy restriction is known to induce a decline in fat oxidation during the postdiet period. Reduced fat oxidation may contribute to weight regain. OBJECTIVE: The present study investigated the effect of the addition of low-intensity exercise training to energy restriction on postdiet fat oxidation and on the contribution of the sympathetic nervous system to fat oxidation. DESIGN: Forty obese men were divided randomly into 2 groups: diet (D) and diet plus exercise (DE). Both groups followed an energy restriction program for 10 wk. Subjects in the DE group also participated in a low-intensity exercise training program [40% maximal oxygen uptake (VO2max)] for 12 wk. Before the intervention and after 12 wk, with subjects at stable body weights, we measured body composition, VO2max, and substrate oxidation at rest, during exercise at 50% VO2max, and during recovery. Measurements were made with and without administration of the beta-adrenergic antagonist propranolol. RESULTS: Both interventions led to significant decreases in body weight, fat mass, and fat-free mass (P < 0.001); these decreases did not differ significantly between the D and DE groups. Neither intervention significantly affected VO2max. The effect of the intervention on the respiratory exchange ratio differed significantly between the D and DE groups [two-way analysis of variance (ANOVA), P < 0.05]. The effect on the beta-adrenergic-mediated respiratory exchange ratio tended to be different between the 2 groups (two-way ANOVA, P = 0.09). CONCLUSION: Addition of low-intensity exercise training to energy restriction counteracts the decline in fat oxidation during the postdiet period.

Adrenergic beta-Antagonists↗

PubMed2001

beta(1)- and beta(2)-Adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men.

The aim of this study was to elucidate the roles of the beta(1)- and the beta(2)-adrenoceptors in thermogenesis and lipid utilization in obesity. The beta(1)-adrenoceptor study was performed in 9 obese and 10 lean men and consisted of 4 30-min periods during which subjects received consecutive infusions of 0, 3, 6, and 9 microg/kg fat-free mass (FFM).min dobutamine. Energy expenditure, lipid oxidation, and plasma nonesterified fatty acids and glycerol concentrations increased similarly in both groups during beta(1)-adrenergic stimulation. The beta(2)-adrenoceptor study was performed in 10 obese and 11 lean men and involved 3 45-min periods during which 0, 50, and 100 ng/kg FFM.min salbutamol were given in combination 1.2 microg/kg FFM.min atenolol (bolus, 50 microg/kg FFM). During beta(2)-adrenergic stimulation, the increases in energy expenditure and plasma nonesterified fatty acids and glycerol concentrations were reduced in the obese group. Furthermore, lipid oxidation significantly increased in the normal weight group, but remained similar in the overweight group. In conclusion, these data suggest that beta(1)-adrenoceptor-mediated metabolic processes are similar in both groups, but beta(2)-adrenoceptor-mediated increases in thermogenesis and lipid utilization are impaired in the obese.

Adult↗