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Biomedical subjects

A Palou

Publications and source records attributed to A Palou.

At least 19 recordsLinked to original sources
PubMed2003

Vitamin A and the regulation of fat reserves.

Beyond their classical nutritional roles, nutrients modify gene expression and function in target cells and, by so doing, affect many fundamental biological processes. An emerging example, which is the focus of this review, is the involvement of vitamin A in the regulation of the level and functioning of body fat reserves. Retinoic acid, the carboxylic acid form of vitamin A, is a transcriptional activator of the genes encoding uncoupling proteins, and results in animals indicate that whole body thermogenic capacity is related to the vitamin A status. Retinoic acid also influences adipocyte differentiation and survival, with high doses inhibiting and low doses promoting adipogenesis of preadipose cells in culture. Moreover, vitamin A status can influence the development and function of adipose tissues in whole animals, with a low vitamin A status favouring increased fat deposition.

Adipocytes↗
PubMed2003

General aspects on the assessment of functional foods in the European Union.

During the last 6 y, the European Union has undergone a profound qualitative change in the focus on food safety problems. In 1997, nine new scientific committees were created, including the Scientific Committee on Food (SCF) and the Scientific Steering Committee (SSC), and were put under the auspices of the Directorate General in charge of defending consumer interests and health. The process is foreseen to be completed by the incorporation in 2003 of all food safety activities of these committees into the European Food Safety Authority (EFSA). Among the immediate challenges in the near future are the scientific and technological developments and the regulatory measures for the so-called 'functional foods', which can positively affect the health and well-being of consumers. Functional foods are a recent phenomenon in Europe and are, as yet, not covered by any specific legislation. The two key aspects in the evaluation of functional foods are safety and efficacy. Whereas safety can be covered under different legislative umbrellas such as novel foods (NFs), foods for particular nutritional purposes, supplements, additives and others, the issue of evaluation of their efficacy is only at a very early stage since the criteria to establish the validity of 'health claims' has not been clearly addressed at a European level.

European Union↗
PubMed2003

Up-regulation of muscle uncoupling protein 3 gene expression in mice following high fat diet, dietary vitamin A supplementation and acute retinoic acid-treatment.

OBJECTIVE: To analyse the impact of vitamin A supplementation of both a normal fat (NF) diet and a high fat (HF) diet and of acute retinoic acid (RA)-treatment on the expression of uncoupling protein 3 (UCP3) in mice. DESIGN: C57BL/6J mice were fed for 18 weeks a NF or a HF diet (10 and 45 energy% as fat, respectively), both with the normal vitamin A content or an excess vitamin A (8 mg and 320 mg retinyl palmitate/kg diet, respectively). Body weight and energy intake were recorded periodically. UCP3 mRNA and UCP3 protein levels in skeletal muscle (soleus/gastrocnemius) were analysed, as well as UCP1, UCP2 and UCP3 mRNA levels in interscapular brown adipose tissue (BAT), and UCP2 mRNA, UCP2 protein and leptin mRNA levels in white adipose tissue (WAT) depots. The effect of acute RA-treatment (100 mg/kg/day, 4 days) on UCP3 mRNA levels in skeletal muscle and BAT of NMRI mice was also assessed. RESULTS: Vitamin A supplementation of a NF diet led to increased levels of UCP3 mRNA and UCP3 protein in muscle, UCP1 mRNA in BAT, and UCP2 mRNA in inguinal WAT, but had no impact on body weight or adiposity of B6 mice. HF diet promoted obesity and increased levels of UCP3 mRNA and UCP3 protein in skeletal muscle, and of the mRNAs for all three UCPs in BAT. Supplementing the HF diet with vitamin A had little effect on the final obesity reached and did not lead to further increases of muscle UCP3 mRNA nor BAT UCP1 mRNA over the levels achieved with the non-supplemented HF diet. Adipose leptin mRNA levels were down regulated after vitamin A supplementation, independently of the fat content of the diet. Up-regulation of muscle, but not BAT, UCP3 mRNA levels was also found after acute RA-treatment in NMRI mice. CONCLUSION: The results provide evidence of a stimulatory effect of retinoids on muscle UCP3 expression in vivo, and a differential retinoid-regulation of the UCP3 gene in muscle and BAT.

Adipose Tissue↗
PubMed2002

Opposite actions of testosterone and progesterone on UCP1 mRNA expression in cultured brown adipocytes.

The brown adipose tissue (BAT) thermogenic response to diet-induced obesity and cold has been found to be gender dependent. In the present work, we aimed to investigate the effects of the main physiological male and female sex hormones, i.e. testosterone, progesterone and 17-beta-estradiol, on the expression of uncoupling protein I (UCP1)--the main mediator of BAT thermogenesis--and on UCP2 and lipid accumulation in rodent brown adipocytes differentiated in culture. Testosterone-treated cells showed fewer and smaller lipid droplets than control cells and a dose-dependent inhibition of UCP1 mRNA expression, under adrenergic stimulation by norepinephrine (NE). These effects were reverted by the androgen receptor antagonist flutamide, suggesting they are dependent, at least in part, on the androgen receptor. Progesterone- and 17-beta-estradiol-treated cells showed more and larger lipid droplets and progesterone stimulated NE-induced UCP1 mRNA expression at the lower concentration tested, but not at higher concentrations, suggesting that for brown adipocytes, this hormone is dose dependent. 17-beta-Estradiol did not have any remarkable effect either on UCP1 or UCP2 mRNA expression. Interestingly, the specific progesterone receptor antagonist RU486 induced UCP1 and UCP2 mRNAs, including UCP1 mRNA expression in non-NE-treated brown adipocytes, suggesting a profound effect of this antiprogestagen on brown adipocyte thermogenic capacity. Thus, are conclude that testosterone, 17-beta-estradiol, progesterone and RU486 have distinct actions on brown adipocytes, thus modulating UCP1 and UCP2 mRNA expression and/or lipid accumulation, and that sex hormones are factors that may explain in part the gender-dependent BAT thermogenic response.

Adipose Tissue, Brown↗
PubMed2002

Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects.

The aim of this study was to identify candidate genes for visceral obesity by screening for genes strongly differentially expressed between human subcutaneous and visceral adipose depots. A cDNA microarray with human adipose-derived cDNAs was used as an initial screening to identify genes that are potentially differentially expressed between human subcutaneous and visceral abdominal fat tissues. For the two best candidates, carboxypeptidase E (CPE) and thrombospondin-1 (THBS1) (EST N72406), real-time RT-PCR was performed to confirm their depot specific expression in extremely obese individuals. Both genes appeared to be strongly differentially expressed, having a higher expression in the visceral depot than in the subcutaneous one. For THBS1, the difference in expression between the depots was greater in women than in men. The involvement of CPE and THBS1 in obesity allows us to suggest that the physiological processes controlled by these genes contribute to depot and gender-related differences in the metabolic complications of obesity.

Adipocytes↗
PubMed2002

[Genetic polymorphisms and new perspectives in the prevention and treatment of obesity].

The prevalence of obesity has increased to an extraordinary degree, especially over the last three decades, so that if these trends persist, practically all of the adult population would be obese in the course of only two generations. On the basis of family and adoption studies, it has been estimated that the genetic component in obesity ranges from 20% to 80%. Thus, the most common forms of obesity would depend on the interaction of multiple genes as well as on the influence of various environmental factors, such as eating behaviour and lifestyle. Although none of these genes potentially involved in the control of body weight seems to be directly responsible for the syndrome, there have been reports of interesting associations between polymorphisms of certain candidate genes and obesity or its metabolic complications. The studies into associations between genotypes and obese phenotype have increased over the last few years and have basically focussed on the genes involved in the control of the energy balance, giving rise to a whole series of results which might constitute the basis for extremely interesting strategies for the prevention and treatment of this serious problem.

Humans↗
PubMed2001

Differential expression of genes for uncoupling proteins 1, 2 and 3 in brown and white adipose tissue depots during rat development.

The different expression patterns of genes for uncoupling proteins (UCPs) 1, 2 and 3 (ucp1, ucp2 and ucp3) were studied in interscapular brown adipose tissue (BAT) and in four white adipose tissue (WAT) depots (epididymal, inguinal, mesenteric and retroperitoneal) in male rats of different ages (18 days-12 months). UCP mRNA expression levels were determined by Northern blotting. In BAT, there were high levels of expression of UCP1 and UCP3 mRNA, but no detectable levels of UCP2 mRNA. Both ucp1 and ucp3 followed a similar expression pattern with age, with high levels in suckling rats which decreased to 50% or less in rats just under 2 months old, declining thereafter until 5 months and then recovering with age. However, an additional peak of expression was observed for ucp3 at the age of 3 months. In WAT, ucp1 expression was rare: occasional expression was found for UCP1 mRNA in the retroperitoneal depot in suckling rats and in the epididymal and inguinal depots in suckling and mature adult rats. ucp2 and ucp3 had different developmental expression patterns, but these were similar for each gene in the different depots studied. UCP3 mRNA was highly expressed in rats soon after birth, it decreased until 3 months, and increased thereafter, except for the mesenteric WAT where ucp3 expression decreased until 7 months before recovering. The fact that changes with age of both ucp1 and ucp3 expression have a similar profile in BAT, which is also similar to the ucp3 and also ucp1 profiles in some WAT depots, might reflect a common regulatory pattern for the expression of these genes, and also a common function. In contrast to ucp1 and ucp3, ucp2 had a peak of expression at about 2 months, and lower expression at 3 months, suggesting different regulation and probably a different role for this UCP.

Adipose Tissue↗
PubMed2001

Weight loss reduces expression of SREBP1c/ADD1 and PPARgamma2 in adipose tissue of obese women.

Weight loss in obese patients, even if moderate, is clearly beneficial for health and implies a reduction in either adipocyte number or volume. This can be regulated by the key adipose transcription factors, sterol-regulatory-element binding protein-1c/adipocyte differentiation and determination factor-1 (SREBP1c/ADD1), peroxisome proliferator-activated receptor-gamma2 (PPARgamma2) and CCAAT-enhancer binding protein-alpha (C/EBPalpha). which regulate the adipocyte metabolism and differentiation process. The present study was undertaken to obtain insights into the expression of these transcription factors during moderate weight loss in humans. In addition, the adipose depot-related differences and the relation to adipose lipoprotein lipase (LPL) expression and plasma lipids were studied. Using quantitative reverse transcription polymerase chain reaction (RT-PCR), the total amount of each adipose transcription factor messenger ribonucleic acid (mRNA) was determined in the subcutaneous or omental adipose tissue after a controlled, 2-month, bodyweight-reduction trial in 11 obese middle-aged women and 17 comparable obese controls. Weight loss (6% of body weight) was associated with reduced serum insulin and plasma triacylglycerols. Adipose tissue PPARgamma2 and SREBP1c/ADD1 mRNA were lower in the weight-loss group than in controls (by 30% and 28%, respectively), whereas the C/EBPalpha mRNA level did not change. Moreover, PPARgamma2 mRNA was lower only in the subcutaneous adipose depot and was related to both adipose tissue lipoprotein lipase (LPL) mRNA and improvement in plasma triacylglycerols in the weight-loss group. Our results suggest a functional role for SREBP1c/ADD1 and PPARgamma2 in the control of energy metabolism in human adipose tissue.

Adipose Tissue↗
PubMed2001

Ontogenesis of leptin expression in different adipose tissue depots in the rat.

Serum leptin levels and leptin mRNA expression by adipose tissue increase with age and are mainly associated with an increase in adiposity. Regional changes in both leptin production and fat distribution contribute to circulating leptin levels and may play a role in the regulation of body weight. a capacity that changes during development. Here, we have studied leptin mRNA expression in four different white adipose tissue depots (epididymal, retroperitoneal, mesenteric, inguinal; namely, EWAT, RWAT, MWAT, IWAT) and in interscapular brown adipose tissue (IBAT). We have also studied their relationship with lipid content and adiposity changes, together with serum leptin levels in male rats at different ages (18, 55, 93, 159, 212, 294 and 355 days). Serum leptin levels increased during development, reaching stable levels at the age of 7 months, and, as expected, were highly correlated with both the adiposity index (r=0.908, P<0.01) and body weight (r=0.906, P<0.01). Leptin mRNA expression also increased with age, following characteristic ontogenic patterns in every adipose tissue depot. The patterns were similar in EWAT and RWAT: leptin expression increased very rapidly during the first 55 days for EWAT and 3 months for RWAT, with a peak in the latter at 7 months, and high expression levels were retained for the rest of the study period. In IWAT and IBAT, leptin expression increased steadily during the 12-month period studied and was significantly lower than levels in EWAT and RWAT. Leptin expression in MWAT increased progressively with age to reach levels close to those of EWAT and RWAT in 10-month-old animals. The pattern of leptin expression in both EWAT and RWAT paralleled their lipid content, and leptin mRNA expression per unit of tissue lipid content was maintained high and constant from a very young age (about 2 and 3 months, respectively). However, the expression of mRNA for leptin (expressed per unit of tissue lipid concentration) in MWAT, IWAT and IBAT increased steadily during the whole period studied, without attaining the maximal levels observed in EWAT and RWAT. MWAT, IWAT and IBAT maintained their capacity to increase leptin mRNA expression in response to an additional accumulation of lipids. Our data demonstrate that there are regional-specific differences and different rates of increase of leptin gene expression within distinct depots of WAT and BAT. These changes cannot be uniquely explained by changes in adiposity or lipid content, implying that there are regional-specific regulatory mechanisms that may depend on the attenuation with age of the beta-adrenergic inhibitory signalling pathway upon leptin expression or on other factors.

Adipose Tissue↗
PubMed2001

Sexual dimorphism in the adrenergic control of rat brown adipose tissue response to overfeeding.

Gender-related differences in the brown adipose tissue (BAT) response to overfeeding rats on a cafeteria diet were studied by assessing the balance between the expression of beta-adrenoceptors (beta1-, beta2-, beta3-AR) and alpha2A-AR and their relation to the expression of uncoupling proteins (UCP1, UCP2, UCP3). Cafeteria diet feeding for 15 days, which involved a similar degree of hyperphagia in both sexes, led to a greater body weight excess in females than in males and a lower activation of thermogenesis. Gender-related differences were found for different adrenoceptor expression and protein levels, which might explain, in part, sex differences in the thermogenic parameters. The lower expression of alpha2A-AR in females than in males could be responsible for the higher expression of UCP1 and thermogenic capacity under non-hyperphagic conditions. However, in a situation of high adrenergic stimulation--as occurs with overfeeding--as there is a preferential recruitment of the beta3-AR by noradrenaline compared with other adrenergic receptors, the higher levels of beta3-AR in males rats than in females could be responsible for the greater thermogenic capacity and the lesser weight gain in males. Thus, the alpha2/beta3 balance in BAT could be a key in the thermogenic control.

Adipose Tissue, Brown↗
PubMed2001

Gender related differences in the effect of aging on blood amino acid compartmentation*

This work has been focused on the study of the variations in blood amino acid compartmentation (plasma and blood cells) with aging, both in men and women. Aging is a situation which, under the influence of gender, involves a decline in body weight functions and variations in energy metabolism with a deterioration of muscular metabolism leading to changes in amino acid handling. We determined the blood levels of individual amino acids in whole blood, plasma compartment and blood cell compartment of 51 men and 51 women. Subjects were classified in three age groups-AG1 (18 to 35 y), AG2 (35-50 y) and AG3 (more than 50 y). Aging was accompanied by significant changes in blood levels of amino acids showing gender-linked differences which were distinct for both blood compartments (plasma and blood cells). In men, aging was accompanied by a drop in blood levels of several amino acids, due mainly to the plasma compartment, whereas in women aging brought about a rise in blood levels of various amino acids mainly in blood cell compartment. This paper contributes to enhancing the physiological importance of the blood cell pool in the handling of amino acids.

Journal Article↗
PubMed2001

Sexual dimorphism in age-related changes in UCP2 and leptin gene expression in subcutaneous adipose tissue in humans.

The influence of age and gender on uncoupling protein 2 (UCP2) expression and its relationship with leptin expression in subcutaneous adipose tissue has been studied in humans. Samples of subcutaneous adipose tissue were obtained from 41 adult subjects (20 women and 21 men), with an age range of 28 to 84 years, and body mass index (BMI) of 19 to 36 Kgm(minus sign2). UCP2 and leptin mRNA expression was determined by northern blot. In women, both leptin and UCP2 expression in the subcutaneous adipose tissue increased significantly with age (r = 0.490 p < 0.05 and r = 0.475 p < 0.05, respectively). In men, in contrast, a negative correlation was found between leptin expression and age (r = minus sign0.678 p < 0.001), while no significant correlation was apparent between UCP2 expression and age (r = minus sign0.077). In addition, there was a positive correlation between UCP2 and leptin expression in women (r = 0.656 p < 0.01). These data show important gender dependent differences in the age-related changes in leptin and UCP2 expression in subcutaneous adipose tissue in humans.

Journal Article↗
PubMed2001

Changes of adiposity in response to vitamin A status correlate with changes of PPAR gamma 2 expression.

OBJECTIVE: To gain insight into the in vivo modulation of the expression of the adipogenic transcription factors PPAR gamma 2, C/EBP alpha, and ADD1/SREBP1c by retinoids and its relationship with whole-body adiposity. RESEARCH METHODS AND PROCEDURES: Three-week-old mice were fed with standard chow or a vitamin A-deficient diet for 10 weeks. During the 4 days immediately before they were killed, the animals were treated either with all-trans retinoic acid (tRA; 100 mg/kg per day, subcutaneously) or vehicle. The specific levels of the mRNAs for the three transcription factors were analyzed in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue and in brown adipose tissue (BAT). Other parameters determined were leptin and UCP2 levels in white adipose tissue depots, total cholesterol and triglyceride serum levels, energy intake, body weight, and adiposity. RESULTS: Vitamin A-deficient diet feeding led to a marked increase of adiposity and to a small increase of body weight. Hypertrophy of white adipose tissue depots correlated with enhanced PPAR gamma 2 expression. Hypertrophy of BAT, in contrast, correlated with a decrease of PPAR gamma 2 expression that may contribute to the known reduced thermogenic potential of BAT under conditions of vitamin A restriction. Treatment with tRA triggered a reduction of adiposity and body weight that correlated with a down-regulation of PPAR gamma 2 expression in all adipose tissues. The effects of tRA were more pronounced in eWAT, where C/EBP alpha and ADD1/SREBP1c levels were also reduced. The response to tRA was impaired in the eWAT and BAT of animals fed the vitamin A-deficient diet. DISCUSSION: The results emphasize the importance of retinoids as physiological regulators of adipose tissue development and function in intact animals.

Adipose Tissue↗
PubMed2001

Sex-dependent dietary obesity, induction of UCPs, and leptin expression in rat adipose tissues.

OBJECTIVE: The aim of this study was to determine the sex-dependent differences in the response of key parameters involved in thermogenesis and control of body weight in brown adipose tissue (BAT) and white adipose tissue (WAT) in postcafeteria-fed rats, a model of dietary obesity. RESEARCH METHODS AND PROCEDURES: BAT and WAT were obtained from male and female control and postcafeteria-fed Wistar rats. Postcafeteria-fed rats were initially fed with cafeteria diet from day 10 of life until day 110 (cafeteria period) and with standard chow diet from then until day 180 of life (postcafeteria period). Body mass and energy intake were evaluated. Biometric parameters were analyzed in interscapular BAT (IBAT). Levels of uncoupling protein 1 (UCP1), alpha(2)-adrenergic receptor (AR), and beta(3)-AR proteins and UCP1, UCP2, UCP3, beta(3)-AR, and leptin mRNAs, in IBAT or WAT, were studied by Western blot and Northern blot analyses, respectively. RESULTS: Rats attained 59% (females) and 39% (males) increase in body weight at the end of the cafeteria period. During the postcafeteria period, the rats showed a loss of body weight, which was higher in females. Postcafeteria-fed female rats also presented higher activation of thermogenic parameters in IBAT, including UCP1, UCP2, and UCP3 mRNAs. Female control rats showed lower levels of both alpha 2 and beta(3)-ARs in BAT compared with male rats, but these levels in postcafeteria-fed female and male rats were the same, because males tended to down-regulate them. Levels of leptin mRNA in response to the postcafeteria state depended on gender and the specific WAT depot studied. DISCUSSION: It is suggested that in postcafeteria-fed female rats, BAT thermogenic capacity becomes more efficiently activated than in males. Female rats also showed a bigger weight loss. The parallel regulation of the levels of UCP2 and UCP3 mRNAs, with respect to UCP1 mRNA, with higher activation in female postcafeteria-fed rats, suggests a possible role of both UCP2 and UCP3 in the regulation of energy expenditure and in the control of body weight. The distinct responses to overweight of alpha 2 and beta(3)-ARs--which were sex dependent--and leptin mRNA--which depended on both sex and WAT depot--also support the different response of thermogenesis-related parameters between overweight males and females.

Adipose Tissue↗
PubMed2000

Chromatographic determination of carotenoids in foods.

In recent years, there has been particular emphasis on obtaining more accurate data on the types and concentrations of carotenoids in foods for various health and nutrition activities. The analysis of carotenoids is complicated because of the diversity and the presence of cis-trans isomeric forms of this group of compounds. In addition, a wide variety of food products of vegetal and animal origin, vegetables and animal samples contain carotenoids, and a great range of carotenoids can be found in these samples. The characteristic conjugated double bond system of carotenoids produces the main problem associated with work and manipulation on carotenoids, that is their particular instability, especially towards light, heat, oxygen and acids. For this reason, several precautions are necessary when handling carotenoids. Another problem associated with analysis of carotenoids is the difficulty in obtaining standard compounds. High-performance liquid chromatographic methods for the determination of carotenoids in foods are reviewed. The sample extraction and treatment, carotenoid purification and standard manipulation are briefly commented on. We present a critical assessment of chromatographic methods developed for the determination of carotenoids in foods. Finally, some methods for carotenoid ester separation are reviewed.

Carotenoids↗
PubMed2000

Obesity: molecular bases of a multifactorial problem.

Obesity could well become the most common health problem of the 21st century. There are more opportunities to consume large quantities of food: big portions of tasty, varied food, at reasonable prices, are available everywhere. Moreover, our bodies are better adapted to combat weight loss than to combat weight gain, since for thousands of years our species evolved in circumstances where nutrients were in short supply. The response of each individual to diet and other environmental factors varies considerably, depending on the characteristics of his/her body weight control mechanisms. The differentiating element in the future, especially as regards the dietary and pharmacological control of obesity, will be knowledge of an individual's possible response depending on his/her genetic background. Obesity can occur as a result of genetic or acquired changes in three main types of biochemical processes, which are the main focus of this review: a)feeding control, which determines the sensations of satiety and hunger through processes that depend on an interplay between internal signals (notably leptin) and environmental factors; b) energy efficiency, in particular the activation of thermogenesis mediated by uncoupling proteins (UCPs) that makes it possible to dissipate part of the energy contained in food as heat instead of accumulating it as fat, and c) adipogenesis, the process by which cells specialised in fat storage (adipocytes) are formed, which is controlled by an interplay of transcription factors, including members of the C/EBP, PPARgamma and ADD families. The knowledge of a growing number of genes and molecules implicated in these three types of processes and of their metabolic relationships is leading toward a molecular understanding of the body weight regulatory system, and is paving the way for new methods of obesity control, especially pharmacological but also nutritional and possibly involving genetic intervention.

Adipose Tissue↗
PubMed2000

Methodological approaches to assess body-weight regulation and aetiology of obesity.

Obesity, which is becoming one of the major health hazards in developed and developing societies, results from a long-term positive energy balance. Body-weight regulation and stability depend on an axis with three interrelated components: food intake, energy expenditure and adipogenesis, although there are still many unknown features concerning fuel homeostasis and energy balance. Biochemical processes are interconnected, and a separate consideration of each component is often useful for methodological purposes and to achieve a better understanding of the whole system. Thus, many different experimental approaches can be applied by using laboratory animals, cell culture or human subjects to unravel the molecular mechanisms which participate in body-weight regulation. Thus, both in vitro (cellular and subcellular models) and in vivo methods have dramatically increased our knowledge of weight control. Several strategies in obesity research are reported here, exploiting the opportunities of the molecular era as well as novel whole-body approaches, which will impact on the development of new targets for obesity management and prevention.

Animals↗