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Biomedical subjects

G Frühbeck

Publications and source records attributed to G Frühbeck.

At least 19 recordsLinked to original sources
PubMed2006

Validity of the leg-to-leg bioimpedance to estimate changes in body fat during weight loss and regain in overweight women: a comparison with multi-compartment models.

OBJECTIVES: To investigate changes in body composition and the validity of the leg-to-leg bioimpedance (LTL) method to measure body fat during active weight loss (WL) and weight regain (WR). DESIGN: Longitudinal, 12-week weight loss intervention (3.3-3.8 MJ/day) and subsequent follow-up at 1 year. SUBJECTS: Fifty-eight adult women aged between 24 and 65 years (mean age: 46.8+/-8.9 years) and with a body mass index (BMI) > or =25 kg/m(2) (mean BMI: 31.6+/-2.5 kg/m(2), range=26.0-48.2 kg/m(2)) participated in the study. MEASUREMENTS: Fat mass (FM) was measured at baseline, 12 weeks, 24 weeks and 52 weeks using three- and four-compartment (4-C) models, air displacement plethysmography (ADP), deuterium dilution - total body water (TBW), dual-energy X-ray absorptiometry (DXA), skinfold thickness (SFT), tetrapolar bioelectrical impedance analysis (T-BIA) and LTL. RESULTS: At the end of the weight loss programme, subjects lost 9.9+/-3.5 kg weight (P<0.001) and 7.6+/-0.5 kg fat (P<0.001) but after 1 year they had regained 4.9+/-3.7 kg of weight and 3.7+/-2.9 kg of fat. The 4-C model showed that FM and TBW accounted for 76.2 and 23.6% of the loss in body mass and 81.8 and 17.7% of the tissue accrued during weight regain, respectively. The estimate of body fat change by LTL relative to multi-compartment models (WL(bias+/-2s.d.)=0.51+/-3.26 kg; WR(bias+/-2s.d.)=-0.25+/-2.30 kg) was similar to ADP, DXA and TBW in both phases but it was better than T-BIA (WL(bias+/-2s.d.)=0.17+/-7.90 kg; WR(bias+/-2s.d.)=-0.29+/-7.59 kg) and skinfold thickness (WL(bias+/-2s.d.)=2.68+/-6.68 kg; WR(bias+/-2s.d.)=-0.84+/-3.80 kg). CONCLUSIONS: Weight loss and regain were associated with minimal changes in lean tissue as measured using multi-compartment models. The LTL system is a useful method to measure body composition changes during clinical weight management programmes.

Adipose Tissue↗
PubMed2006

Variability of appetite control mechanisms in response to 9 weeks of progressive overfeeding in humans.

BACKGROUND: The current epidemic of obesity demonstrates that mechanisms for maintaining human energy balance are readily subverted by adverse environmental conditions. The critical elements of this dysregulation are poorly understood. Most previous research into what regulates the intake side of the energy balance equation has been handicapped by the use of short-term within-day experimental tests. OBJECTIVE: We enrolled six non-obese men to a 17-week protocol involving three 21 days periods of progressive overfeeding (+20, +40 and +60%) separated by free diet periods to test for compensatory satiety. RESULTS: Responses to overfeeding differed markedly with evidence of 'compensators' and 'non-compensators', but on average, subsequent food intake was stimulated rather than suppressed after overfeeding in spite of markedly elevated body fat (+13%) and fasting leptin (+116%). DISCUSSION: The inefficient response of in-built appetite control mechanisms emphasizes the need to adopt intentional cognitive restraint in the modern environment when food is plentiful.

Adipose Tissue↗
PubMed2004

The adipose tissue as a source of vasoactive factors.

Obesity is associated with increased incidence of cardiovascular mortality. However, the mechanisms that link increased fat mass with hypercholesterolemia, hypertension, endothelial dysfunction and coronary heart disease have not been fully elucidated. Unravelling the diverse neuroendocrine systems, which regulate energy balance and body fat has been a long-standing challenge in biology, with obesity as an increasingly important public health focus. Until recently, the adipocyte has been considered only a passive tissue for the storage of excess energy in the form of fat. However, there is now compelling evidence that adipocytes act as endocrine, secretory cells. It has been shown that several hormones, growth factors and cytokines are actually expressed in white adipose tissue. In a dynamic view of the adipocyte a wide range of signals emanates from white adipose tissue such as tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and their respective soluble receptors. White adipose tissue also secretes important regulators of lipoprotein metabolism like lipoprotein lipase (LPL), apolipoprotein E (apoE) and cholesteryl ester transfer protein (CETP). The increasing number of products secreted by adipocytes also includes leptin, estrogen, angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), tissue factor and transforming growth factor-beta (TGF-beta). Nitric oxide synthase (NOS) has been also reported to be expressed in white adipose tissue. Acylation stimulating protein (ASP), adipophilin, adipoQ, adipsin, monobutyrin, agouti protein and factors related to pro-inflammatory and immune processes have also been shown to be released by white adipocytes. Since blood vessels express receptors for most of the adipocyte-derived factors, adipose tissue seems to play a key role in cardiovascular physiology through the existence of a network of local and systemic signals. The current knowledge in this field will be reviewed in the broader perspective of cardiovascular physiology and pathophysiology.

Adipose Tissue↗
PubMed2003

Adipose tissue as an endocrine organ: role of leptin and adiponectin in the pathogenesis of cardiovascular diseases.

Obesity, the most common nutritional disorder in industrial countries, is associated with increased cardiovascular mortality and morbidity. Nevertheless, the molecular basis linking obesity with cardiovascular disturbances have not yet been fully clarified. Recent advances in the biology of adipose tissue indicate that it is not simply an energy storage organ, but also a secretory organ, producing a variety of bioactive substances, including leptin and adiponectin, that may influence the function as well as the structural integrity of the cardiovascular system. Leptin, besides being a satiety signal for the central nervous system and to be related to insulin and glucose metabolism, may also play an important role in regulating vascular tone because of the widespread distribution of functional receptors in the vascular cells. On the other hand, the more recently discovered protein, adiponectin, seems to play a protective role in experimental models of vascular injury, in probable relation to its ability to suppress the attachment of monocytes to endothelial cells, which is an early event in the atherosclerotic process. There is already considerable evidence linking altered production of some adipocyte hormones with the cardiovascular complications of obesity. Therefore, the knowledge of alterations in the endocrine function of adipose tissue may help to further understand the high cardiovascular risk associated with obesity.

Adiponectin↗
PubMed2003

Leptin does not respond to 48 h fat deposition or mobilization in women.

OBJECTIVE: To test the hypothesis that acute responses of plasma leptin concentration to energy balance manipulation are mediated by fat flux. DESIGN: Ten healthy women aged 31-63 y, mass 48-113.5 kg, fat mass 8.5-62.5 kg, were studied for 3 days in a whole-body calorimeter on two occasions. After a control day (D1) during which energy balance was maintained, diet was manipulated to induce fat deposition (FD) or mobilization (FM) of 50 g/day for 2 days (D2 & D3). A difference totalling of 194+/-18.6 g fat was achieved between manipulations without significant effects on carbohydrate or protein balance. Fasting plasma leptin was measured on D2 and D4. RESULTS: After the control day plasma leptin concentration averaged 19.01+/-9.8 ng/ml, and was found to be linearly related to body fat mass. After 2 days manipulation of fat balance, leptin concentrations were 21.4+/-10.3 ng/ml (FD) and 21.2+/-11.3 ng/ml (FM). There was no significant difference between treatments in either control day or postmanipulation leptin concentrations, nor did the treatments induce any differences in glucose or insulin concentration responses. CONCLUSION: Although in states of energy balance leptin concentration is linearly related to fat mass, acute modulation of leptin concentration during energy imbalance is not mediated by fat flux.

Adipose Tissue↗
PubMed2002

Interactions between an alpha2-adrenergic antagonist and a beta3-adrenergic agonist on the expression of UCP2 and UCP3 in rats.

This experimental trial was devised to assess whether selective beta3-adrenergic receptor (AR) stimulation and simultaneous blockade of alpha2-AR would affect thermoregulation. With this purpose, the individual and combined administration of a beta-AR agonist, trecadrine, and an alpha2-AR antagonist, yohimbine, were evaluated. Yohimbine produced a marked decrease (p < 0.001) in body temperature one hour after administration (5 mg kg(-1), i.p.) and blocked the thermogenic effect of trecadrine (1 mg kg(-1), i.p.) when simultaneously administered. Uncoupling protein-2 expression in skeletal muscle was downregulated (p < 0.05) by trecadrine, while yohimbine had no effect. White adipose tissue UCP2 and muscle UCP3 were not modified by either trecadrine or yohimbine administration. Liver UCP2 mRNA expression was significantly decreased by yohimbine (p < 0.05). However, this downregulation does not seem to explain the reduction in temperature produced by yohimbine given the fact that trecadrine produced a similar downregulation of hepatic UCP2 (p < 0.05). The present work indicates that alpha2-AR antagonism blocks the thermogenic effects mediated by beta3-AR stimulation, contrary to our expectations, suggesting a possible interplay between both mechanisms. Moreover, these effects are not apparently explained by changes in UCP2 and UCP3.

Adipose Tissue↗
PubMed2001

Rapid in vivo PGC-1 mRNA upregulation in brown adipose tissue of Wistar rats by a beta(3)-adrenergic agonist and lack of effect of leptin.

Peroxisome proliferator-activated receptor-gamma coactivator-1 (PGC-1) is highly expressed in brown adipose tissue (BAT) and plays an important role in adaptive thermogenesis. The aim of this study was to assess the acute effect of a beta(3)-adrenergic agonist (Trecadrine) and leptin on the expression of PGC-1 and PPARgamma2 mRNA in BAT. Trecadrine produced a marked increase (4.5-fold) in PGC-1 mRNA compared to controls (P<0.001) without changes in PPARgamma2 mRNA, whereas leptin administration did not alter either PGC-1 or PPARgamma2 expression. These results show that selective stimulation of the beta(3)-adrenoceptor rapidly upregulates the expression of PGC-1 in brown adipocytes without a concomitant increase in PPARgamma2. Moreover, our results show that PGC-1 and PPARgamma2 expression in BAT seems not to be acutely regulated by leptin.

Adipose Tissue, Brown↗
PubMed2001

Modulation of the leptin-induced white adipose tissue lipolysis by nitric oxide.

The present study tested the hypothesis that nitric oxide (NO) is involved in the leptin-induced stimulation of lipolysis. The effect of intravenous (iv) administration of leptin (10, 100 and 1000 microg/kg body weight) or vehicle on serum NO concentrations and glycerol release from white adipocytes of Wistar rats was examined. One hour after injection, the three leptin doses tested increased serum NO concentrations 15.1%, 23.4% and 60.0%, respectively (P<.001 vs. baseline). The effect of leptin on NO concentrations was significantly dose dependent on linear trend testing (P=.0001). Simple linear regression analysis showed that the lipolytic rate measured was significantly correlated with serum NO concentrations (P=.0025; r=.52). In order to gain further insight into the potential underlying mechanisms, the effect of leptin on lipolysis was studied in the setting of nitric oxide synthase (NOS) inhibition or acute ganglionic blockade. The stimulatory effect of leptin on lipolysis was significantly decreased (P<.05) under NOS inhibition. On the contrary, the leptin-induced lipolysis was unaltered in pharmacologically induced ganglionic blockade. The lack of effect on isoproterenol-, forskolin- and dibutyryl-cyclic AMP-stimulated lipolysis suggests that leptin does not interfere with the signal transduction pathway at the beta-adrenergic receptor, the adenylate cyclase and the protein kinase A levels. These findings suggest that NO is a potential regulator of leptin-induced lipolysis.

Adipose Tissue↗
PubMed2001

A heliocentric view of leptin.

Leptin is significantly broadening our understanding of the mechanisms underlying neuroendocrine function. Initially, based on a rather static view of the hormone, most investigations focused on the effects of leptin on food intake control and body-weight homeostasis, with attention primarily focused on the implications of leptin as a lipostatic factor and central satiety agent. However, the almost ubiquitous distribution of leptin receptors in peripheral tissues provided a fertile area for investigation and a more dynamic view of leptin started to unfold. This adipocyte-derived circulating peptidic hormone, with a tertiary structure resembling that of members of the long-chain helical cytokine family, has generated an enormous interest in the interaction as well as integration between brain targets and peripheral signals. Considerable evidence for systemic effects of leptin on specific tissues and metabolic pathways indicates that leptin operates both directly and indirectly to orchestrate complex pathophysiological processes. Disentangling the biochemical and molecular mechanisms in which leptin is involved represents one of the major challenges ahead.

Animals↗
PubMed2001

Leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes.

The aim of the present study was to gain insight into the signaling pathway used by leptin to stimulate lipolysis. The lipolytic rate of white adipocytes from sex- and age-matched lean (+/+) and fa/fa rats was determined in the absence or presence of leptin together with a number of agents acting at different levels of the signaling cascade. Leptin did not modify FSK-, dbcAMP-, and IBMX-stimulated lipolysis. Lipolysis can also be maximally stimulated by lowering media adenosine levels with adenosine deaminase (ADA), i.e., in the ligand-free state. Although ADA produced near maximal lipolysis in adipocytes of lean animals, only half of the maximal lipolytic rate (50.9+/-3.2%) was achieved in fat cells from fa/fa rats (P=0.0034). In adipocytes from lean animals preincubated with ADA, leptin caused a concentration-related stimulation of lipolysis (P=0.0001). However, leptin had no effect on the lipolytic activity of adipocytes in the ligand-free state from fa/fa rats. The adenosine A1 receptor agonist CPA effectively inhibited basal lipolysis in both lean and obese adipocytes (P=0.0001 and P=0.0090, respectively). Leptin had no effect on the lipolytic rate of adipocytes isolated from fa/fa rats and preincubated with CPA. When adipocytes were incubated with the A1 receptor antagonist DPCPX, a significant increase in glycerol release was observed in fa/fa fat cells (P=0.009), whereas cells isolated from lean rats showed no differences to ADA-stimulated lipolysis. After pretreatment with PTX, which inactivates receptor-mediated Gi function, adipocytes of obese rats became as responsive to the stimulatory actions of ISO as cells from lean rats (P=0.0090 vs. ISO in fa/fa rats; P=0.2416 vs. lean rats, respectively). PTX treatment of lean cells, however, did not alter their response to this lipolytic agent. It can be concluded that the lipolytic effect of leptin is located at the adenylate cyclase/Gi proteins level and that leptin-induced lipolysis opposes the tonic inhibition of endogenous adenosine in white adipocytes.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Rationale for the existence of additional adipostatic hormones.

Parabiosis studies with obese rodents demonstrated that circulating factors are involved in the long-term control of food intake and energy balance. More than 40 years ago it was hypothesized that rats made obese by hypothalamic or dietary means, as well as genetically obese fa/fa rats and db/db mice, produce a circulating factor that either inhibits food intake or acts metabolically to reduce the fat content of non-obese ad libitum-fed partners. However, none of these obese rodents showed a significant change in weight when parabiosed to a normal animal. It was therefore postulated that these obese rodents produced a circulating lipostatic factor but were unable to respond to it. In contrast, genetically obese ob/ob mice were thought to be deficient in the circulating signal, as they lost weight when parabiosed to lean or obese db/db mice. The discovery of leptin suggested that the circulating lipostatic signal had been identified. However, a closer look at the outcome of the parabiotic studies reveals that leptin alone does not explain all of the findings of the parabiotic experiments. Another (or more than one) as yet unidentified factor(s) may be involved in energy balance regulation. The evidence for the existence of further leptin-like hormones comes from observations in which the direct effect of leptin has been eliminated or can be excluded.

Adipose Tissue↗
PubMed2001

The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation.

The ability to ensure continuous availability of energy despite highly variable supplies in the environment is a major determinant of the survival of all species. In higher organisms, including mammals, the capacity to efficiently store excess energy as triglycerides in adipocytes, from which stored energy could be rapidly released for use at other sites, was developed. To orchestrate the processes of energy storage and release, highly integrated systems operating on several physiological levels have evolved. The adipocyte is no longer considered a passive bystander, because fat cells actively secrete many members of the cytokine family, such as leptin, tumor necrosis factor-alpha, and interleukin-6, among other cytokine signals, which influence peripheral fuel storage, mobilization, and combustion, as well as energy homeostasis. The existence of a network of adipose tissue signaling pathways, arranged in a hierarchical fashion, constitutes a metabolic repertoire that enables the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess.

Adipocytes↗
PubMed2001

Perspectives in the therapeutic use of leptin.

The cloning and characterisation of the protein encoded by the ob gene, called leptin, has represented an enormous advance in the knowledge we have at the present time on the control of appetite and the regulation of body weight. Animal experiments have shown that this adipocyte-derived hormone informs the hypothalamus about the magnitude of fat stores and induces changes in eating behaviour and thermogenesis directed to maintain nutritional homeostasis. Besides the CNS and adipose tissue, other tissues like the gonads, adrenals, pancreas, blood vessels, immune cells and bone are also targets for leptin action, setting the basis for the pleiotropic character of leptin. In contrast to ob(-)/ob(-) mice, which have leptin deficiency, obese patients usually exhibit hyperleptinaemia due to leptin resistance of uncertain aetiology. Patients with congenital leptin deficiency show a dramatic response to recombinant leptin therapy in terms of body weight and fat reduction. However, in contrast to animals, no thermogenic effect has been demonstrated in humans treated with leptin. Leptin-resistant obese subjects display a heterogeneous response to leptin treatment, though some patients achieve a significant weight loss when receiving high doses. New formulations are being tried with different success rates. Before leptin can play a role in the treatment of obesity, more studies are needed to discover which is the adequate dose, which the best route and form of administration and how we can select the patients who will benefit from this particular therapy. The development of new leptin analogues with high penetrating capacity to cross the blood-brain barrier and the investigation of other approaches to overcome the leptin resistance are awaited. Future applications of leptin may be directed to the treatment of infertility, wound healing and bone remodelling among others.

Animals↗
PubMed2001

Divergent effects of an alpha2-adrenergic antagonist on lipolysis and thermogenesis: interactions with a beta3-adrenergic agonist in rats.

This study was undertaken in order to test the hypothesis that selective beta3-AR stimulation and simultaneous blockade of alpha2-AR would result in an increase of lipolysis and thermogenesis in rats. Incubation of isolated white adipocytes with the alpha2-AR antagonist yohimbine produced a concentration-dependent increase in glycerol release (P<0.001) for all assayed concentrations (10-12-10-6 M) and potentiated the lipolytic effect of the beta3-AR agonist Trecadrine. However, in vivo administration of yohimbine produced a marked decrease in body temperature (1.3-1.5 degrees C, P<0.001) and blocked the thermogenic effect of Trecadrine when simultaneously administered. A similar response was observed for whole body oxygen consumption. Furthermore, yohimbine did not modify brown adipose tissue oxygen consumption, but blocked the beta3-AR-mediated increase triggered by Trecadrine. Brown adipose tissue UCP-2 and -3 mRNA expression was not changed by yohimbine. In conclusion, the present work indicates that in vitro alpha2-AR blockade by yohimbine potentiates the beta3-AR-mediated stimulation of lipolysis. On the other hand, in vivo alpha2-AR antagonism blocks the thermogenic effects mediated by beta3-AR stimulation, suggesting a possible interplay between the receptors.

Adipocytes↗